Is CRYGA p.Arg140Gln (c.419G>A) pathogenic?

CRYGA p.Arg140Gln (c.419G>A) is classified Uncertain significance in CRYGA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0834); Ultra-rare (popmax 0.0312%, eas).

How common is CRYGA p.Arg140Gln (c.419G>A) in the general population?

CRYGA p.Arg140Gln (c.419G>A) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about CRYGA p.Arg140Gln (c.419G>A)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

CRYGA p.Arg140Gln

c.419G>A · rs573473213 · VCV3077895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -3.8
Regional constraint	o/e 1.16	unconstrained · MANE · 2,749 bp · p 0.016 · regional, not allelic
Overall
CADD	17.3	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 0.0312% East Asian · 14/44,860 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00428% 69/1,612,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,204
Finnishnot grpmax-eligible	0.00937%	10,667
South Asian	0.00879%	11,383
African / African-American	0.00534%	18,738
Admixed American	0.005%	19,994
Remaining individualsnot grpmax-eligible	0.0048%	20,823
European (non-Finnish)	0.00263%	38,035

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: CRYGA
Protein: p.Arg140Gln
Coding: c.419G>A
MANE Select: NM_014617
dbSNP: rs573473213
Type: single nucleotide variant
Location: chr2:208160910 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.14
Residue 140: the beta/gamma crystallin 'greek key' 4 domain

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

Similar variants

CRYGA p.Arg140Leu Uncertain significance ★ ⚠ same residue
CRYGA p.Arg99Ter Benign ★★ same type
CRYGA p.Ala110Thr Uncertain significance ★ ⚠ same type
CRYGA p.Arg142Gln Uncertain significance ★ ⚠ same type
CRYGA p.Arg153Ser Uncertain significance ★ ⚠ same type
CRYGA p.Arg15His Uncertain significance ★ ⚠ same type
CRYGA p.Arg169Gln Uncertain significance ★ ⚠ same type
CRYGA p.Arg169Trp Uncertain significance ★ ⚠ same type

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/cryga-p-arg140gln (accessed [today's date]).

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