Is MYO7A p.Arg814His (c.2441G>A) pathogenic?

MYO7A p.Arg814His (c.2441G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.2796); Very rare (popmax 0.00683%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg814His (c.2441G>A)?

MYO7A p.Arg814His (c.2441G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg814His (c.2441G>A) in the general population?

MYO7A p.Arg814His (c.2441G>A) is very rare (popmax 0.00683%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg814His (c.2441G>A)?

AlphaMissense predicts likely benign (score 0.2796) — an in-silico prediction, not a clinical call.

MYO7A p.Arg814His

c.2441G>A · rs1220715086 · VCV1389068

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00683%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2796	likely benign
REVEL	0.695	pathogenic-leaning
SaProt	LLR -11.55	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	29.5	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 0.00683% African / African-American · 5/73,194 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.00123% 19/1,547,604 alleles · very rare exomes 14/1,395,396 · genomes 5/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00683%	14,639
Finnishnot grpmax-eligible	0.00374%	26,703
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,674
East Asian	0.00243%	41,130
Admixed American	0.00194%	51,554
South Asian	0.00119%	84,178
European (non-Finnish)	0.000696%	143,584

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.Arg814His
Coding: c.2441G>A
MANE Select: NM_000260
dbSNP: rs1220715086
Type: single nucleotide variant
Location: chr11:77179808 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 814: 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.Arg814= Likely benign ★ 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
MYO7A p.Ala162Thr 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-arg814his (accessed [today's date]).

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