Is MYO7A p.Arg900His (c.2699G>A) pathogenic?

MYO7A p.Arg900His (c.2699G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1985); Very rare (popmax 0.00554%, nfe).

How common is MYO7A p.Arg900His (c.2699G>A) in the general population?

MYO7A p.Arg900His (c.2699G>A) is very rare (popmax 0.00554%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg900His (c.2699G>A)?

AlphaMissense predicts likely benign (score 0.1985) — an in-silico prediction, not a clinical call.

MYO7A p.Arg900His

c.2699G>A · rs781790828 · VCV1420034

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00554%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1985	likely benign
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -8.12	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.7	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 0.00554% European (non-Finnish) · 64/1,154,416 alleles

Filtering AF 0.00444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.00455% 71/1,561,432 alleles · very rare exomes 69/1,409,182 · genomes 2/152,250 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00554%	18,038
Remaining individualsnot grpmax-eligible	0.00495%	20,205
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,754
East Asian	0.00238%	41,972
South Asian	0.00235%	42,494

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.Arg900His
Coding: c.2699G>A
MANE Select: NM_000260
dbSNP: rs781790828
Type: single nucleotide variant
Location: chr11:77181384 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 900: the 'sah' region

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

Similar variants

MYO7A p.Arg900Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg900Leu 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-arg900his (accessed [today's date]).

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