Is MYO7A p.Arg2209Trp (c.6625C>T) pathogenic?

MYO7A p.Arg2209Trp (c.6625C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-02). AlphaMissense: ambiguous (0.4387); Very rare (popmax 0.00808%, afr).

How common is MYO7A p.Arg2209Trp (c.6625C>T) in the general population?

MYO7A p.Arg2209Trp (c.6625C>T) is very rare (popmax 0.00808%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg2209Trp (c.6625C>T)?

AlphaMissense predicts ambiguous (score 0.4387) — an in-silico prediction, not a clinical call.

MYO7A p.Arg2209Trp

c.6625C>T · rs771103993 · VCV1450483

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00808%, afr)

Computational evidence

Protein change
AlphaMissense	0.4387	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -10.91	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP 1.8
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.2	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 0.00808% African / African-American · 6/74,290 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0024%

Overall 0.00189% 30/1,583,760 alleles · very rare exomes 24/1,431,568 · genomes 6/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00808%	12,382
South Asian	0.0058%	17,244
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,056
Remaining individualsnot grpmax-eligible	0.00325%	30,746
East Asian	0.0023%	43,422
Admixed American	0.00181%	55,330
European (non-Finnish)	0.0012%	83,209

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.Arg2209Trp
Coding: c.6625C>T
MANE Select: NM_000260
dbSNP: rs771103993
Type: single nucleotide variant
Location: chr11:77214673 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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

Similar variants

MYO7A p.Arg2209Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg2209Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Arg2209= Likely benign ★ 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

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-arg2209trp (accessed [today's date]).

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