Is MYO7B p.Arg1755Gln (c.5264G>A) pathogenic?

MYO7B p.Arg1755Gln (c.5264G>A) is classified Likely benign in MYO7B (ClinVar, Single submitter, 2 submitters; last evaluated 2022-12-01). AlphaMissense: likely benign (0.1015); Rare (popmax 0.764%, nfe).

How common is MYO7B p.Arg1755Gln (c.5264G>A) in the general population?

MYO7B p.Arg1755Gln (c.5264G>A) is rare (popmax 0.764%, nfe) (gnomAD).

What do computational predictors say about MYO7B p.Arg1755Gln (c.5264G>A)?

AlphaMissense predicts likely benign (score 0.1015) — an in-silico prediction, not a clinical call.

MYO7B p.Arg1755Gln

c.5264G>A · rs190699169 · VCV2651335

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1015 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.764%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1015	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -8.74	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 8.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1729Q vs ClinVar R1755Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.764% European (non-Finnish) · 9,010/1,179,518 alleles

Filtering AF 0.751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.745%

Overall 0.639% 10,296/1,611,878 alleles · rare exomes 9,642/1,459,498 · genomes 654/152,380 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.988%	101
Amishnot grpmax-eligible	0.877%	114
European (non-Finnish)grpmax	0.764%	131
Middle Eastern	0.611%	164
Remaining individualsnot grpmax-eligible	0.559%	179
Admixed American	0.497%	201
South Asian	0.152%	660
African / African-American	0.14%	715
Finnishnot grpmax-eligible	0.0942%	1,061

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1755Gln
Coding: c.5264G>A
MANE Select: NM_001393586
dbSNP: rs190699169
Type: single nucleotide variant
Location: chr2:127632260 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1729 UniProt numbering: the myth4 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region; an α-helix

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

Similar variants

MYO7B p.Arg1755Trp Uncertain significance ★ ⚠ same residue
MYO7B p.Thr349Met Uncertain significance ★★ ⚠ same type
MYO7B p.Ile1309Val Benign ★★ same type
MYO7B p.Val1556Ile Benign ★★ same type
MYO7B p.Val1876= Benign ★★ same type
MYO7B p.Ala1010Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1092Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1109Thr Uncertain significance ★ ⚠ 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/myo7b-p-arg1755gln (accessed [today's date]).

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