Is CRCP p.Pro57Ser (c.169C>T) pathogenic?

CRCP p.Pro57Ser (c.169C>T) is classified Uncertain significance in CRCP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.2144); Very rare (popmax 0.00638%, nfe).

How common is CRCP p.Pro57Ser (c.169C>T) in the general population?

CRCP p.Pro57Ser (c.169C>T) is very rare (popmax 0.00638%, nfe) (gnomAD).

What do computational predictors say about CRCP p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.2144) — an in-silico prediction, not a clinical call.

CRCP p.Pro57Ser

c.169C>T · VCV3269437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00638%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2144	likely benign
REVEL	0.759	pathogenic-leaning
SaProt	LLR -13.02	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 3.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 37 kb · p 0.00048 · regional, not allelic
Overall
CADD	24.3	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 0.00638% European (non-Finnish) · 75/1,175,956 alleles

Filtering AF 0.00521% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00475%

Overall 0.00543% 79/1,453,654 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00638%	15,679
Remaining individualsnot grpmax-eligible	0.00323%	31,007
African / African-American	0.00271%	36,944

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: CRCP
Protein: p.Pro57Ser
Coding: c.169C>T
MANE Select: NM_014478
Type: single nucleotide variant
Location: chr7:66134304 (GRCh38)
Gene constraint: LOEUF 1.397 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.31 · 29 PDB
Residue 57: a turn

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

Similar variants

CRCP p.Glu144Lys Uncertain significance ★★ ⚠ same type
CRCP p.Ala72Thr Uncertain significance ★ ⚠ same type
CRCP p.Ala9Val Uncertain significance ★ ⚠ same type
CRCP p.Arg27Cys Uncertain significance ★ ⚠ same type
CRCP p.Arg59Gly Uncertain significance ★ ⚠ same type
CRCP p.Arg90Gln Uncertain significance ★ ⚠ same type
CRCP p.Arg90Trp Uncertain significance ★ ⚠ same type
CRCP p.Asn135His 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/crcp-p-pro57ser (accessed [today's date]).

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