Is MYO7B p.Glu1649= (c.4947G>A) pathogenic?

MYO7B p.Glu1649= (c.4947G>A) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 31.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Glu1649= (c.4947G>A)?

MYO7B p.Glu1649= (c.4947G>A) is associated with MYO7B-related disorder (ClinVar).

MYO7B p.Glu1649=

Q: How common is MYO7B p.Glu1649= (c.4947G>A) in the general population?

MYO7B p.Glu1649= (c.4947G>A) is common (popmax 31.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4947G>A · rs13025791 · VCV3056512

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

MYO7B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.006	GERP -3.5, phastCons 0.35
Overall
CADD	2.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.4% South Asian · 28,339/90,250 alleles

Filtering AF 31.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 31%

Overall 19.2% 307,940/1,599,750 alleles · common exomes 283,693/1,447,474 · genomes 24,247/152,276 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	31.4%	3
Finnishnot grpmax-eligible	22.1%	5
European (non-Finnish)	19.7%	5
Middle Eastern	19.1%	5
Remaining individualsnot grpmax-eligible	18.6%	5
Ashkenazi Jewishnot grpmax-eligible	15.2%	7
East Asian	13.4%	7
Admixed American	12%	8
African / African-American	6.52%	15
Amishnot grpmax-eligible	3.07%	33

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.Glu1649=
Coding: c.4947G>A
MANE Select: NM_001393586
dbSNP: rs13025791
Type: single nucleotide variant
Location: chr2:127631215 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1649: the myth4 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

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-glu1649 (accessed [today's date]).

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