Is MYO7B p.Gly1053Ser (c.3157G>A) pathogenic?

MYO7B p.Gly1053Ser (c.3157G>A) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-01). AlphaMissense: likely benign (0.0705); Low-frequency (popmax 1.08%, afr); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Gly1053Ser (c.3157G>A)?

MYO7B p.Gly1053Ser (c.3157G>A) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Gly1053Ser (c.3157G>A) in the general population?

MYO7B p.Gly1053Ser (c.3157G>A) is low-frequency (popmax 1.08%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Gly1053Ser (c.3157G>A)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

MYO7B p.Gly1053Ser

c.3157G>A · rs199654311 · VCV3038043

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -5.84	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 0.15	GERP -2.7
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	0.061	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 1.08% African / African-American · 813/74,968 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.998%

Overall 0.0601% 967/1,608,382 alleles · low-frequency exomes 482/1,456,110 · genomes 485/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.08%	92
Admixed American	0.103%	972
Remaining individualsnot grpmax-eligible	0.0931%	1,074
Middle Eastern	0.0838%	1,193
East Asian	0.00449%	22,252
South Asian	0.00443%	22,577
European (non-Finnish)	0.00204%	49,067

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.Gly1053Ser
Coding: c.3157G>A
MANE Select: NM_001393586
dbSNP: rs199654311
Type: single nucleotide variant
Location: chr2:127609981 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1053: the 'mediates interaction with anks4b' region; the myth4 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.Gly1053Asp Uncertain significance ★ ⚠ same residue
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

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-gly1053ser (accessed [today's date]).

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