Is CRYAB p.Val152Ala (c.455T>C) pathogenic?

CRYAB p.Val152Ala (c.455T>C) is classified Likely benign in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0596); Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Val152Ala (c.455T>C)?

CRYAB p.Val152Ala (c.455T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is CRYAB p.Val152Ala (c.455T>C) in the general population?

CRYAB p.Val152Ala (c.455T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CRYAB p.Val152Ala (c.455T>C)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

CRYAB p.Val152Ala

c.455T>C · VCV3497346

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,623 bp · p 0.098 · regional, not allelic
Overall
CADD	11.1	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 0.00223% East Asian · 1/44,890 alleles

Overall 6.84e-05% 1/1,461,654 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.Val152Ala
Coding: c.455T>C
MANE Select: NM_001289808
Type: single nucleotide variant
Location: chr11:111908837 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 152: the shsp domain; 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.Val152Leu Uncertain significance ★ ⚠ same residue
HSPB2 p.His152Arg 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

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-val152ala (accessed [today's date]).

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