Is MYO7A p.Arg2061Gln (c.6182G>A) pathogenic?

MYO7A p.Arg2061Gln (c.6182G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.126); Ultra-rare (popmax 0.0163%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg2061Gln (c.6182G>A)?

MYO7A p.Arg2061Gln (c.6182G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg2061Gln (c.6182G>A) in the general population?

MYO7A p.Arg2061Gln (c.6182G>A) is ultra-rare (popmax 0.0163%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg2061Gln (c.6182G>A)?

AlphaMissense predicts likely benign (score 0.126) — an in-silico prediction, not a clinical call.

MYO7A p.Arg2061Gln

c.6182G>A · rs202175478 · VCV2143031

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.126 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0163%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.126	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0163% South Asian · 14/85,992 alleles

Filtering AF 0.00982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00519% 82/1,581,234 alleles · ultra-rare exomes 76/1,429,074 · genomes 6/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0163%	6,142
Remaining individualsnot grpmax-eligible	0.0114%	8,757
African / African-American	0.00539%	18,562
European (non-Finnish)	0.00481%	20,785
Admixed American	0.00182%	55,088

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.Arg2061Gln
Coding: c.6182G>A
MANE Select: NM_000260
dbSNP: rs202175478
Type: single nucleotide variant
Location: chr11:77211282 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2061: 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

Similar variants

MYO7A p.Arg2061Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr Uncertain significance ★★ ⚠ 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-arg2061gln (accessed [today's date]).

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