Is CRISP3 p.Ala40Ser (c.118G>T) pathogenic?

CRISP3 p.Ala40Ser (c.118G>T) is classified Uncertain significance in CRISP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Very rare (popmax 0.0067%, eas).

How common is CRISP3 p.Ala40Ser (c.118G>T) in the general population?

CRISP3 p.Ala40Ser (c.118G>T) is very rare (popmax 0.0067%, eas) (gnomAD).

CRISP3 p.Ala40Ser

c.118G>T · VCV3836397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -3.9
Regional constraint	o/e 1.10	unconstrained · MANE · 16 kb · p 0.097 · regional, not allelic
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,808 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000249% 4/1,606,406 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,936
Remaining individualsnot grpmax-eligible	0.00161%	62,248

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: CRISP3
Protein: p.Ala40Ser
Coding: c.118G>T
MANE Select: NM_006061
Type: single nucleotide variant
Location: chr6:49736501 (GRCh38)
Gene constraint: LOEUF 1.477 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.65

Full CRISP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRISP3 p.Ala118Val Uncertain significance ★ same type
CRISP3 p.Ala125Thr Uncertain significance ★ same type
CRISP3 p.Ala168Val Uncertain significance ★ same type
CRISP3 p.Ala249Thr Uncertain significance ★ same type
CRISP3 p.Ala25Val Uncertain significance ★ same type
CRISP3 p.Arg103Leu Uncertain significance ★ same type
CRISP3 p.Arg244Gly Uncertain significance ★ same type
CRISP3 p.Asn134Asp 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/crisp3-p-ala40ser (accessed [today's date]).

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