Is MYO7A p.Ala601Thr (c.1801G>A) pathogenic?

MYO7A p.Ala601Thr (c.1801G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1568); Ultra-rare (popmax 0.0283%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Ala601Thr (c.1801G>A)?

MYO7A p.Ala601Thr (c.1801G>A) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Ala601Thr (c.1801G>A) in the general population?

MYO7A p.Ala601Thr (c.1801G>A) is ultra-rare (popmax 0.0283%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Ala601Thr (c.1801G>A)?

AlphaMissense predicts likely benign (score 0.1568) — an in-silico prediction, not a clinical call.

MYO7A p.Ala601Thr

c.1801G>A · rs782481491 · VCV306170

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.1568 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.1568	likely benign
REVEL	0.282	benign-leaning
SaProt	LLR -5.83	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 2.9	GERP -0.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	20.5	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 0.0283% European (non-Finnish) · 326/1,150,900 alleles

Filtering AF 0.0257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.0237% 369/1,556,130 alleles · ultra-rare exomes 349/1,403,928 · genomes 20/152,202 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0283%	3,530
East Asian	0.0267%	3,751
Admixed American	0.0231%	4,331
Remaining individualsnot grpmax-eligible	0.0149%	6,695
Finnishnot grpmax-eligible	0.0118%	8,475
Ashkenazi Jewishnot grpmax-eligible	0.00697%	14,354
African / African-American	0.00273%	36,623

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.Ala601Thr
Coding: c.1801G>A
MANE Select: NM_000260
dbSNP: rs782481491
Type: single nucleotide variant
Location: chr11:77172751 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 601: the myosin motor domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal dominant nonsyndromic hearing loss 11 nonsyndromic genetic hearing loss Usher syndrome type 1B

Similar variants

MYO7A p.Ala601fs Likely pathogenic ★ same residue
MYO7A p.Ala601= 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
MYO7A p.Arg853His Likely 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-ala601thr (accessed [today's date]).

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