Is MYO7B p.Arg1290Gln (c.3869G>A) pathogenic?

MYO7B p.Arg1290Gln (c.3869G>A) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-11). AlphaMissense: likely benign (0.0646); Low-frequency (popmax 3.85%, afr); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Arg1290Gln (c.3869G>A)?

MYO7B p.Arg1290Gln (c.3869G>A) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Arg1290Gln (c.3869G>A) in the general population?

MYO7B p.Arg1290Gln (c.3869G>A) is low-frequency (popmax 3.85%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Arg1290Gln (c.3869G>A)?

AlphaMissense predicts likely benign (score 0.0646) — an in-silico prediction, not a clinical call.

MYO7B p.Arg1290Gln

c.3869G>A · rs2245408 · VCV3038394

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0646 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.85%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0646	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 0.75, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	19.33	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 R1264Q vs ClinVar R1290Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.85% African / African-American · 2,871/74,588 alleles

Filtering AF 3.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.68%

Overall 0.223% 3,561/1,593,602 alleles · low-frequency exomes 1,846/1,441,294 · genomes 1,715/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.85%	26
Admixed American	0.417%	240
Remaining individualsnot grpmax-eligible	0.373%	268
Middle Eastern	0.232%	431
European (non-Finnish)	0.0164%	6,098
South Asian	0.0137%	7,306
East Asian	0.00457%	21,872

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.Arg1290Gln
Coding: c.3869G>A
MANE Select: NM_001393586
dbSNP: rs2245408
Type: single nucleotide variant
Location: chr2:127624142 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1264 UniProt numbering: the 'mediates interaction with anks4b' region; a UniProt-annotated variant site (in); the ferm 1 domain

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

Disease context

MYO7B-related disorder

Similar variants

MYO7B p.Ala397Ser Uncertain significance ⚠ same condition
MYO7B c.1081-10G>T Benign same condition
MYO7B c.1691-7T>C Benign same condition
MYO7B c.2339+4C>T Benign same condition
MYO7B c.4333+8C>A Likely benign same condition
MYO7B c.5714-7C>T Benign same condition
MYO7B c.5821-8T>C Benign same condition
MYO7B c.6123+9T>C Benign same condition

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-arg1290gln (accessed [today's date]).

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