Is MYO7A p.Ser1767Leu (c.5300C>T) pathogenic?

MYO7A p.Ser1767Leu (c.5300C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1655); Very rare (popmax 0.00969%, amr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ser1767Leu (c.5300C>T)?

MYO7A p.Ser1767Leu (c.5300C>T) is associated with Inborn genetic diseases, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ser1767Leu (c.5300C>T) in the general population?

MYO7A p.Ser1767Leu (c.5300C>T) is very rare (popmax 0.00969%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Ser1767Leu (c.5300C>T)?

AlphaMissense predicts likely benign (score 0.1655) — an in-silico prediction, not a clinical call.

MYO7A p.Ser1767Leu

c.5300C>T · rs757896867 · VCV952138

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00969%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1655	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.56, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.2	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 0.00969% Admixed American · 5/51,576 alleles

Filtering AF 0.00621% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0058%

Overall 0.00644% 100/1,552,818 alleles · very rare exomes 94/1,400,566 · genomes 6/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00969%	10,315
European (non-Finnish)	0.00757%	13,209
African / African-American	0.00546%	18,305
Remaining individualsnot grpmax-eligible	0.00499%	20,025
South Asian	0.00119%	84,160

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.Ser1767Leu
Coding: c.5300C>T
MANE Select: NM_000260
dbSNP: rs757896867
Type: single nucleotide variant
Location: chr11:77203191 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1767: the myth4 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: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

Similar variants

MYO7A p.Ser1767Ter Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Ser1767= 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-ser1767leu (accessed [today's date]).

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