Is CRYAB p.Arg120Ser (c.360G>T) pathogenic?

CRYAB p.Arg120Ser (c.360G>T) is classified Uncertain significance in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Arg120Ser (c.360G>T)?

CRYAB p.Arg120Ser (c.360G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is CRYAB p.Arg120Ser (c.360G>T) in the general population?

CRYAB p.Arg120Ser (c.360G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAB p.Arg120Ser (c.360G>T)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

CRYAB p.Arg120Ser

c.360G>T · VCV4869430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 1% in CRYAB
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -13.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,623 bp · p 0.098 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRYAB
Protein: p.Arg120Ser
Coding: c.360G>T
MANE Select: NM_001289808
Type: single nucleotide variant
Location: chr11:111908932 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 120: the shsp domain; a UniProt-annotated variant site (in mfm2a; decreased interactions with wild-type cryaa and cryab but increased interactions with wild-type crybb2 and crygc; cytoplasmic aggregation); a β-strand

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.Arg120Lys Uncertain significance ★ ⚠ same residue
CRYAB p.Arg120Gly Pathogenic 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-arg120ser (accessed [today's date]).

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