Is CRIP2 p.Ser111Arg (c.331A>C) pathogenic?

CRIP2 p.Ser111Arg (c.331A>C) is classified Uncertain significance in CRIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.7888); Ultra-rare (popmax 0.0106%, eas).

How common is CRIP2 p.Ser111Arg (c.331A>C) in the general population?

CRIP2 p.Ser111Arg (c.331A>C) is ultra-rare (popmax 0.0106%, eas) (gnomAD).

What do computational predictors say about CRIP2 p.Ser111Arg (c.331A>C)?

AlphaMissense predicts likely pathogenic (score 0.7888) — an in-silico prediction, not a clinical call.

CRIP2 p.Ser111Arg

c.331A>C · rs782228637 · VCV2297514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7888 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7888	likely pathogenic
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 0.17, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 4,787 bp · p 4.9e-07 · regional, not allelic
Overall
CADD	23.9	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 0.0106% East Asian · 4/37,734 alleles

Filtering AF 0.00357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00216%

Overall 0.000417% 6/1,437,494 alleles · ultra-rare exomes 3/1,286,464 · genomes 3/151,030 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0106%	9,434
South Asian	0.00147%	67,956
European (non-Finnish)	9.04e-05%	1,106,675

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: CRIP2
Protein: p.Ser111Arg
Coding: c.331A>C
MANE Select: NM_001312
dbSNP: rs782228637
Type: single nucleotide variant
Location: chr14:105478865 (GRCh38)
Gene constraint: LOEUF 1.553 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.78 · 1 PDB
Residue 111: the 'disordered' region

Full CRIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP2 p.Ala113Val Uncertain significance ★ ⚠ same type
CRIP2 p.Ala166Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Ala82Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Ala96Gly Uncertain significance ★ ⚠ same type
CRIP2 p.Ala98Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Arg128His Uncertain significance ★ ⚠ same type
CRIP2 p.Arg148Gly Uncertain significance ★ ⚠ same type
CRIP2 p.Arg148Trp 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/crip2-p-ser111arg (accessed [today's date]).

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