Is MYO7A p.Pro1785Ser (c.5353C>T) pathogenic?

MYO7A p.Pro1785Ser (c.5353C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-04). AlphaMissense: likely pathogenic (0.8714); Very rare (popmax 0.00939%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Pro1785Ser (c.5353C>T)?

MYO7A p.Pro1785Ser (c.5353C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Pro1785Ser (c.5353C>T) in the general population?

MYO7A p.Pro1785Ser (c.5353C>T) is very rare (popmax 0.00939%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Pro1785Ser (c.5353C>T)?

AlphaMissense predicts likely pathogenic (score 0.8714) — an in-silico prediction, not a clinical call.

MYO7A p.Pro1785Ser

c.5353C>T · rs985510524 · VCV1949493

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8714 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00939%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8714	likely pathogenic
REVEL	0.799	moderately pathogenic-leaning
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.2	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 0.00939% African / African-American · 7/74,548 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.000624% 10/1,601,414 alleles · very rare exomes 8/1,449,190 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00939%	10,650
Admixed American	0.00341%	29,283
East Asian	0.00226%	44,160

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.Pro1785Ser
Coding: c.5353C>T
MANE Select: NM_000260
dbSNP: rs985510524
Type: single nucleotide variant
Location: chr11:77204102 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1785: the myth4 2 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

Similar variants

MYO7A p.Pro1785= Likely benign ★★ same residue
MYO7A p.Pro1785Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Pro1785Thr Uncertain significance ★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ 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-pro1785ser (accessed [today's date]).

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