Is MYO7A p.Arg702His (c.2105G>A) pathogenic?

MYO7A p.Arg702His (c.2105G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-01). AlphaMissense: likely benign (0.1149); Very rare (popmax 0.00878%, sas).

How common is MYO7A p.Arg702His (c.2105G>A) in the general population?

MYO7A p.Arg702His (c.2105G>A) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg702His (c.2105G>A)?

AlphaMissense predicts likely benign (score 0.1149) — an in-silico prediction, not a clinical call.

MYO7A p.Arg702His

c.2105G>A · rs555579952 · VCV2144044

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1149 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1149	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.62, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	19.58	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 0.00878% South Asian · 8/91,070 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00428% 69/1,613,186 alleles · very rare exomes 61/1,460,904 · genomes 8/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.005%	20,007
European (non-Finnish)	0.00441%	22,690
African / African-American	0.00267%	37,517

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.Arg702His
Coding: c.2105G>A
MANE Select: NM_000260
dbSNP: rs555579952
Type: single nucleotide variant
Location: chr11:77175382 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 702: the myosin motor domain

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

Similar variants

MYO7A p.Arg702= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Arg702Cys 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
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His 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-arg702his (accessed [today's date]).

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