Is CRYAB p.Arg120Gly (c.358A>G) pathogenic?

CRYAB p.Arg120Gly (c.358A>G) is classified Pathogenic in CRYAB (ClinVar, No assertion criteria, 2 submitters; last evaluated 2006-04-07). AlphaMissense: likely pathogenic (0.9969); Absent from gnomAD v4.1; Associated with myofibrillar myopathy 2.

What condition is associated with CRYAB p.Arg120Gly (c.358A>G)?

CRYAB p.Arg120Gly (c.358A>G) is associated with myofibrillar myopathy 2 (ClinVar).

How common is CRYAB p.Arg120Gly (c.358A>G) in the general population?

CRYAB p.Arg120Gly (c.358A>G) is absent from gnomAD v4.1 (gnomAD).

How is Alpha-B crystallin-related late-onset myopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CRYAB p.Arg120Gly (c.358A>G)?

AlphaMissense predicts likely pathogenic (score 0.9969) — an in-silico prediction, not a clinical call.

CRYAB p.Arg120Gly

c.358A>G · rs104894201 · VCV16953

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 2

Computational evidence

Protein change
AlphaMissense	0.9969	likely pathogenic ✓ concordant with ClinVar · top 3% in CRYAB
REVEL	0.954	strongly pathogenic-leaning
SaProt	LLR -14.25	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 3.5	GERP -2.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,623 bp · p 0.098 · regional, not allelic
Overall
CADD	25.9	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

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.Arg120Gly
Coding: c.358A>G
MANE Select: NM_001289808
dbSNP: rs104894201
Type: single nucleotide variant
Location: chr11:111908934 (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

myofibrillar myopathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alpha-B crystallin-related late-onset myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CRYAB p.Arg120Lys Uncertain significance ★ ⚠ same residue
CRYAB p.Arg120Ser Uncertain significance ★ ⚠ same residue
CRYAB p.Ala168Gly Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg107Cys Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg11Gly Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg123Trp Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg157His Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg22His 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-arg120gly (accessed [today's date]).

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