Is MYO7A p.Pro1677Ser (c.5029C>T) pathogenic?

MYO7A p.Pro1677Ser (c.5029C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-28). AlphaMissense: likely benign (0.0853); Rare (popmax 0.108%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Pro1677Ser (c.5029C>T)?

MYO7A p.Pro1677Ser (c.5029C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Pro1677Ser (c.5029C>T) in the general population?

MYO7A p.Pro1677Ser (c.5029C>T) is rare (popmax 0.108%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Pro1677Ser (c.5029C>T)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

MYO7A p.Pro1677Ser

c.5029C>T · rs535102352 · VCV833697

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	19.91	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 0.108% Admixed American · 65/59,986 alleles

Filtering AF 0.0872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0795%

Overall 0.00428% 69/1,613,264 alleles · rare exomes 67/1,461,076 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.108%	923
Remaining individualsnot grpmax-eligible	0.00641%	15,611

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.Pro1677Ser
Coding: c.5029C>T
MANE Select: NM_000260
dbSNP: rs535102352
Type: single nucleotide variant
Location: chr11:77201624 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Pro1677Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Pro1677= 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-pro1677ser (accessed [today's date]).

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