Is MYO7A p.Ser607Leu (c.1820C>T) pathogenic?

MYO7A p.Ser607Leu (c.1820C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-18). AlphaMissense: ambiguous (0.5474); Ultra-rare (popmax 0.0193%, eas); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Ser607Leu (c.1820C>T)?

MYO7A p.Ser607Leu (c.1820C>T) is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ser607Leu (c.1820C>T) in the general population?

MYO7A p.Ser607Leu (c.1820C>T) is ultra-rare (popmax 0.0193%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Ser607Leu (c.1820C>T)?

AlphaMissense predicts ambiguous (score 0.5474) — an in-silico prediction, not a clinical call.

MYO7A p.Ser607Leu

c.1820C>T · rs782598897 · VCV1982954

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5474 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, eas)

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.5474	ambiguous
REVEL	0.425	indeterminate
SaProt	LLR -5.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.7	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 0.0193% East Asian · 8/41,348 alleles

Filtering AF 0.00958% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00698%

Overall 0.00301% 47/1,558,924 alleles · ultra-rare exomes 44/1,406,686 · genomes 3/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0193%	5,168
Middle Eastern	0.0173%	5,780
European (non-Finnish)	0.00312%	32,002
South Asian	0.00237%	42,168

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.Ser607Leu
Coding: c.1820C>T
MANE Select: NM_000260
dbSNP: rs782598897
Type: single nucleotide variant
Location: chr11:77172770 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 607: the myosin motor domain

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

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2

Similar variants

MYO7A p.Ser607Ter Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Ser607= Likely benign ★★ same residue
MYO7A p.Ser607Pro Uncertain significance ★ ⚠ 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-ser607leu (accessed [today's date]).

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