Is MYO7A p.Ala1563Val (c.4688C>T) pathogenic?

MYO7A p.Ala1563Val (c.4688C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.0826); Very rare (popmax 0.0033%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ala1563Val (c.4688C>T)?

MYO7A p.Ala1563Val (c.4688C>T) is associated with Inborn genetic diseases, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Ala1563Val (c.4688C>T) in the general population?

MYO7A p.Ala1563Val (c.4688C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Ala1563Val (c.4688C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

MYO7A p.Ala1563Val

c.4688C>T · rs569752467 · VCV2157911

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.2	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 0.0033% South Asian · 3/90,806 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000558% 9/1,612,596 alleles · very rare exomes 9/1,460,274 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,269
Remaining individualsnot grpmax-eligible	0.0016%	62,450
European (non-Finnish)	0.000424%	235,921

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.Ala1563Val
Coding: c.4688C>T
MANE Select: NM_000260
dbSNP: rs569752467
Type: single nucleotide variant
Location: chr11:77199654 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1563: the ferm 1 domain

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: autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Ala1563= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Ala1563Thr Uncertain significance ★ ⚠ same residue
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
MYO7A p.Glu968Asp 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-ala1563val (accessed [today's date]).

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