Is MYO7B p.Arg2058Gln (c.6173G>A) pathogenic?

MYO7B p.Arg2058Gln (c.6173G>A) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.1035); Very rare (popmax 0.00892%, eas).

How common is MYO7B p.Arg2058Gln (c.6173G>A) in the general population?

MYO7B p.Arg2058Gln (c.6173G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about MYO7B p.Arg2058Gln (c.6173G>A)?

AlphaMissense predicts likely benign (score 0.1035) — an in-silico prediction, not a clinical call.

MYO7B p.Arg2058Gln

c.6173G>A · VCV3401652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1035	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.4	GERP -1.8, phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R2032Q vs ClinVar R2058Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,818 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00329% 53/1,612,672 alleles · very rare exomes 47/1,460,560 · genomes 6/152,112 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,204
European (non-Finnish)	0.00407%	24,571
Remaining individualsnot grpmax-eligible	0.0016%	62,424

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: MYO7B
Protein: p.Arg2058Gln
Coding: c.6173G>A
MANE Select: NM_001393586
Type: single nucleotide variant
Location: chr2:127636594 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 2032 UniProt numbering: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/myo7b-p-arg2058gln (accessed [today's date]).

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