Is CRYAB p.Glu165= (c.495G>A) pathogenic?

CRYAB p.Glu165= (c.495G>A) is classified Likely benign in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Glu165= (c.495G>A)?

CRYAB p.Glu165= (c.495G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is CRYAB p.Glu165= (c.495G>A) in the general population?

CRYAB p.Glu165= (c.495G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CRYAB p.Glu165=

c.495G>A · VCV3269645

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.216	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP 0.48, phastCons 0.075
Overall
CADD	7.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,460,950 alleles · very rare

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: CRYAB
Protein: p.Glu165=
Coding: c.495G>A
MANE Select: NM_001289808
Type: single nucleotide variant
Location: chr11:111908797 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 165: the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYAB p.Glu165Asp Uncertain significance ★ ⚠ same residue
CRYAB c.324+4T>A Uncertain significance ★★ same condition
CRYAB c.325-2A>G Uncertain significance ★★ same condition
CRYAB c.-5C>T Uncertain significance ★★ same condition
CRYAB p.Ala171Thr Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg11Cys Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg123Gln Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg157Cys Uncertain significance ★★ ⚠ 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/cryab-p-glu165 (accessed [today's date]).

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