Is CRIP2 p.Ser104Arg (c.312C>A) pathogenic?

CRIP2 p.Ser104Arg (c.312C>A) is classified Uncertain significance in CRIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely benign (0.2968); Ultra-rare (popmax 0.0135%, afr).

How common is CRIP2 p.Ser104Arg (c.312C>A) in the general population?

CRIP2 p.Ser104Arg (c.312C>A) is ultra-rare (popmax 0.0135%, afr) (gnomAD).

What do computational predictors say about CRIP2 p.Ser104Arg (c.312C>A)?

AlphaMissense predicts likely benign (score 0.2968) — an in-silico prediction, not a clinical call.

CRIP2 p.Ser104Arg

c.312C>A · rs1263319205 · VCV2596223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2968 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2968	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.2	GERP -2.3
Regional constraint	o/e 1.29	unconstrained · MANE · 4,787 bp · p 4.9e-07 · regional, not allelic
Overall
CADD	5.592	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 0.0135% African / African-American · 9/66,430 alleles

Filtering AF 0.00705% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00519%

Overall 0.000772% 11/1,425,594 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0135%	7,381
European (non-Finnish)	0.000182%	550,146

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.Ser104Arg
Coding: c.312C>A
MANE Select: NM_001312
dbSNP: rs1263319205
Type: single nucleotide variant
Location: chr14:105478846 (GRCh38)
Gene constraint: LOEUF 1.553 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.78 · 1 PDB
Residue 104: the 'disordered' region; a modified residue (phosphoserine)

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-ser104arg (accessed [today's date]).

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