Is CRACD p.Ser975Pro (c.2923T>C) pathogenic?

CRACD p.Ser975Pro (c.2923T>C) is classified Uncertain significance in CRACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely pathogenic (0.6107); Ultra-rare (popmax 0.0213%, nfe).

How common is CRACD p.Ser975Pro (c.2923T>C) in the general population?

CRACD p.Ser975Pro (c.2923T>C) is ultra-rare (popmax 0.0213%, nfe) (gnomAD).

What do computational predictors say about CRACD p.Ser975Pro (c.2923T>C)?

AlphaMissense predicts likely pathogenic (score 0.6107) — an in-silico prediction, not a clinical call.

CRACD p.Ser975Pro

c.2923T>C · rs778081617 · VCV3077116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6107	likely pathogenic
REVEL	0.323	indeterminate
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.00032 · regional, not allelic
Overall
CADD	25.0	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 0.0213% European (non-Finnish) · 251/1,179,956 alleles

Filtering AF 0.0191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.016% 259/1,613,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0213%	4,701
Remaining individualsnot grpmax-eligible	0.008%	12,496
Finnishnot grpmax-eligible	0.00469%	21,335

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: CRACD
Protein: p.Ser975Pro
Coding: c.2923T>C
MANE Select: NM_001393381
dbSNP: rs778081617
Type: single nucleotide variant
Location: chr4:56316425 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.09
Residue 975: a modified residue (phosphoserine); the 'disordered' region

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

Similar variants

CRACD p.Ala1035Gly Uncertain significance ★ ⚠ same type
CRACD p.Ala1105Val Uncertain significance ★ ⚠ same type
CRACD p.Ala1116Asp Uncertain significance ★ ⚠ same type
CRACD p.Ala1149Pro Uncertain significance ★ ⚠ same type
CRACD p.Ala1149Val Uncertain significance ★ ⚠ same type
CRACD p.Ala1190Val Uncertain significance ★ ⚠ same type
CRACD p.Ala283Val Uncertain significance ★ ⚠ same type
CRACD p.Ala303Thr 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/cracd-p-ser975pro (accessed [today's date]).

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