Is MYO7A p.Arg2070Trp (c.6208C>T) pathogenic?

MYO7A p.Arg2070Trp (c.6208C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-17). AlphaMissense: likely benign (0.2516); Ultra-rare (popmax 0.0108%, amr).

How common is MYO7A p.Arg2070Trp (c.6208C>T) in the general population?

MYO7A p.Arg2070Trp (c.6208C>T) is ultra-rare (popmax 0.0108%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg2070Trp (c.6208C>T)?

AlphaMissense predicts likely benign (score 0.2516) — an in-silico prediction, not a clinical call.

MYO7A p.Arg2070Trp

c.6208C>T · rs371848786 · VCV1419789

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2516	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -12.12	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 0.66, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.0108% Admixed American · 6/55,352 alleles

Filtering AF 0.00468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00315%

Overall 0.00303% 48/1,582,778 alleles · ultra-rare exomes 39/1,430,640 · genomes 9/152,138 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0108%	9,225
East Asian	0.00928%	10,780
South Asian	0.00348%	28,715
Remaining individualsnot grpmax-eligible	0.00326%	30,679
European (non-Finnish)	0.00275%	36,404
African / African-American	0.00135%	74,246

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.Arg2070Trp
Coding: c.6208C>T
MANE Select: NM_000260
dbSNP: rs371848786
Type: single nucleotide variant
Location: chr11:77211308 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2070: the ferm 2 domain; an α-helix

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

Similar variants

MYO7A p.Arg2070Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg2070= 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
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-arg2070trp (accessed [today's date]).

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