Is CRYGC p.Arg115His (c.344G>A) pathogenic?

CRYGC p.Arg115His (c.344G>A) is classified Uncertain significance in CRYGC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely benign (0.0973); Ultra-rare (popmax 0.045%, amr); Associated with Inborn genetic diseases.

What condition is associated with CRYGC p.Arg115His (c.344G>A)?

CRYGC p.Arg115His (c.344G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CRYGC p.Arg115His (c.344G>A) in the general population?

CRYGC p.Arg115His (c.344G>A) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about CRYGC p.Arg115His (c.344G>A)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

CRYGC p.Arg115His

c.344G>A · rs530871884 · VCV2345146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.492	indeterminate
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,586 bp · p 0.96 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.045% Admixed American · 27/59,992 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00421% 68/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,222
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00534%	18,722
South Asian	0.00439%	22,770
European (non-Finnish)	0.00212%	47,201

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.Arg115His
Coding: c.344G>A
MANE Select: NM_020989
dbSNP: rs530871884
Type: single nucleotide variant
Location: chr2:208128384 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 115: an α-helix; the beta/gamma crystallin 'greek key' 3 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.Arg115Cys Uncertain significance ★ ⚠ same residue
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.Arg147Lys Uncertain significance ★ same condition
CRYGC p.Arg153Gln Uncertain significance ★ ⚠ same condition
CRYGC p.Arg32His 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-arg115his (accessed [today's date]).

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