Is MYO7A p.Arg834His (c.2501G>A) pathogenic?

MYO7A p.Arg834His (c.2501G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). AlphaMissense: likely benign (0.1056); Very rare (popmax 0.00714%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg834His (c.2501G>A)?

MYO7A p.Arg834His (c.2501G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg834His (c.2501G>A) in the general population?

MYO7A p.Arg834His (c.2501G>A) is very rare (popmax 0.00714%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg834His (c.2501G>A)?

AlphaMissense predicts likely benign (score 0.1056) — an in-silico prediction, not a clinical call.

MYO7A p.Arg834His

c.2501G>A · rs569858361 · VCV1398286

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1056 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00714%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1056	likely benign
REVEL	0.455	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00714% South Asian · 6/83,990 alleles

Filtering AF 0.00306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.000454% 7/1,541,196 alleles · very rare exomes 6/1,388,824 · genomes 1/152,372 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00714%	13,998
African / African-American	0.00137%	73,152

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.Arg834His
Coding: c.2501G>A
MANE Select: NM_000260
dbSNP: rs569858361
Type: single nucleotide variant
Location: chr11:77179868 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 834: the iq 4 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.Arg834Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg834Leu 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
MYO7A p.Ala1563Val 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-arg834his (accessed [today's date]).

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