Is CRYGC p.Arg32His (c.95G>A) pathogenic?

CRYGC p.Arg32His (c.95G>A) is classified Uncertain significance in CRYGC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1787); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with CRYGC p.Arg32His (c.95G>A)?

CRYGC p.Arg32His (c.95G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CRYGC p.Arg32His (c.95G>A) in the general population?

CRYGC p.Arg32His (c.95G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CRYGC p.Arg32His (c.95G>A)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

CRYGC p.Arg32His

c.95G>A · VCV4234711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -12.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,586 bp · p 0.96 · regional, not allelic
Overall
CADD	19.73	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 0.00833% Admixed American · 5/60,026 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00186% 30/1,614,236 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00446%	22,446
African / African-American	0.00266%	37,527
European (non-Finnish)	0.00144%	69,415
South Asian	0.0011%	91,088

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: CRYGC
Protein: p.Arg32His
Coding: c.95G>A
MANE Select: NM_020989
Type: single nucleotide variant
Location: chr2:208129598 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 32: the beta/gamma crystallin 'greek key' 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYGC p.Arg77His Uncertain significance ★★ ⚠ same condition
CRYGC p.Asn138Ser Uncertain significance ★★ ⚠ same condition
CRYGC p.Met160Thr Uncertain significance ★★ ⚠ same condition
CRYGC p.Ala164Val Uncertain significance ★ ⚠ same condition
CRYGC p.Arg115Cys Uncertain significance ★ ⚠ same condition
CRYGC p.Arg115His Uncertain significance ★ ⚠ same condition
CRYGC p.Arg147Lys Uncertain significance ★ same condition
CRYGC p.Arg153Gln 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/crygc-p-arg32his (accessed [today's date]).

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