Is CRYGD p.Ser40Arg (c.120C>A) pathogenic?

CRYGD p.Ser40Arg (c.120C>A) is classified Uncertain significance in CRYGD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.6942); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CRYGD p.Ser40Arg (c.120C>A)?

CRYGD p.Ser40Arg (c.120C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CRYGD p.Ser40Arg (c.120C>A) in the general population?

CRYGD p.Ser40Arg (c.120C>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CRYGD p.Ser40Arg (c.120C>A)?

AlphaMissense predicts likely pathogenic (score 0.6942) — an in-silico prediction, not a clinical call.

CRYGD p.Ser40Arg

c.120C>A · rs374192743 · VCV3077907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6942	likely pathogenic
REVEL	0.614	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,797 bp · p 0.94 · regional, not allelic
Overall
CADD	21.2	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 0.00534% African / African-American · 4/74,894 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,612,278 alleles · very rare exomes 4/1,460,068 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
Admixed American	0.00167%	59,858

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: CRYGD
Protein: p.Ser40Arg
Coding: c.120C>A
MANE Select: NM_006891
dbSNP: rs374192743
Type: single nucleotide variant
Location: chr2:208124244 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 40: the beta/gamma crystallin 'greek key' 1 domain; a β-strand

Full CRYGD 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

CRYGD p.Ser40Cys Uncertain significance ★ ⚠ same residue
CRYGD p.Ser40= Likely benign ★ same residue
CRYGD p.Asn119Ser Uncertain significance ★★ ⚠ same condition
CRYGD p.Arg117Cys Uncertain significance ★ ⚠ same condition
CRYGD p.Arg153His Uncertain significance ★ ⚠ same condition
CRYGD p.Asn138Lys Uncertain significance ★ same condition
CRYGD p.Asn50Lys Uncertain significance ★ ⚠ same condition
CRYGD p.His84Asp 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/crygd-p-ser40arg (accessed [today's date]).

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