Is MYO7A p.Ala2083Thr (c.6247G>A) pathogenic?

MYO7A p.Ala2083Thr (c.6247G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-06-18). AlphaMissense: likely benign (0.1032); Rare (popmax 0.13%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ala2083Thr (c.6247G>A)?

MYO7A p.Ala2083Thr (c.6247G>A) is associated with Inborn genetic diseases, hearing loss disorder, Meniere disease (ClinVar).

How common is MYO7A p.Ala2083Thr (c.6247G>A) in the general population?

MYO7A p.Ala2083Thr (c.6247G>A) is rare (popmax 0.13%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Ala2083Thr (c.6247G>A)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

MYO7A p.Ala2083Thr

c.6247G>A · rs41298759 · VCV178496

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.13%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.7	GERP 0.55, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.13% South Asian · 118/91,072 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.0431% 695/1,613,770 alleles · rare exomes 655/1,461,508 · genomes 40/152,262 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.142%	705
South Asiangrpmax	0.13%	772
Remaining individualsnot grpmax-eligible	0.0528%	1,893
European (non-Finnish)	0.0406%	2,463
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,502
Finnishnot grpmax-eligible	0.00938%	10,664
African / African-American	0.00933%	10,718
East Asian	0.00223%	44,866

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYO7A
Protein: p.Ala2083Thr
Coding: c.6247G>A
MANE Select: NM_000260
dbSNP: rs41298759
Type: single nucleotide variant
Location: chr11:77211830 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2083: the ferm 2 domain; an α-helix

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hearing loss disorder Meniere disease Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

Similar variants

MYO7A p.Ala2083Val Uncertain significance ★ ⚠ same residue
MYO7A p.Ala2083fs Likely pathogenic ★ same residue
MYO7A p.Ala2083= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/myo7a-p-ala2083thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown