Is MYO7A p.Arg853Ser (c.2557C>A) pathogenic?

MYO7A p.Arg853Ser (c.2557C>A) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely pathogenic (0.8738); No allele count reported in gnomAD v4.1 (AN 1,532,352).

How common is MYO7A p.Arg853Ser (c.2557C>A) in the general population?

MYO7A p.Arg853Ser (c.2557C>A) is no allele count reported in gnomAD v4.1 (AN 1,532,352) (gnomAD).

What do computational predictors say about MYO7A p.Arg853Ser (c.2557C>A)?

AlphaMissense predicts likely pathogenic (score 0.8738) — an in-silico prediction, not a clinical call.

MYO7A p.Arg853Ser

c.2557C>A · rs2135473615 · VCV1962149

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8738 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,532,352)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8738	likely pathogenic ✓ concordant with ClinVar
REVEL	0.746	pathogenic-leaning
SaProt	LLR -12.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,532,352). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MYO7A
Protein: p.Arg853Ser
Coding: c.2557C>A
MANE Select: NM_000260
dbSNP: rs2135473615
Type: single nucleotide variant
Location: chr11:77179924 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 853: the iq 5 domain; a UniProt-annotated variant site (in dfna11; disturb calmodulin/myo7a binding)

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

Similar variants

MYO7A p.Arg853His Likely pathogenic ★★★ same residue
MYO7A p.Arg853Cys Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Arg853Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Arg853_His856delinsHisArgLeuAsn Uncertain significance ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type

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-arg853ser (accessed [today's date]).

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