Is CSRP1 p.Pro2Leu (c.5C>T) pathogenic?

CSRP1 p.Pro2Leu (c.5C>T) is classified Uncertain significance in CSRP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.6562); Very rare (popmax 0.00534%, afr).

How common is CSRP1 p.Pro2Leu (c.5C>T) in the general population?

CSRP1 p.Pro2Leu (c.5C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CSRP1 p.Pro2Leu (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.6562) — an in-silico prediction, not a clinical call.

CSRP1 p.Pro2Leu

c.5C>T · VCV4235303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6562 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6562	likely pathogenic
REVEL	0.462	indeterminate
SaProt	LLR -13.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 12 kb · p 0.043 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00534% African / African-American · 4/74,902 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00329% 53/1,612,704 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,726
East Asian	0.00446%	22,446
European (non-Finnish)	0.00382%	26,200
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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: CSRP1
Protein: p.Pro2Leu
Coding: c.5C>T
MANE Select: NM_004078
Type: single nucleotide variant
Location: chr1:201496299 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49

Full CSRP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSRP1 p.Ala129= Benign ★★ same type
CSRP1 p.Tyr62= Benign ★★ same type
CSRP1 p.Ala188Val Uncertain significance ★ ⚠ same type
CSRP1 p.Arg118Cys Uncertain significance ★ ⚠ same type
CSRP1 p.Arg118His Uncertain significance ★ ⚠ same type
CSRP1 p.Arg121Gln Uncertain significance ★ ⚠ same type
CSRP1 p.Asn174Ile Uncertain significance ★ ⚠ same type
CSRP1 p.Asn43His 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/csrp1-p-pro2leu (accessed [today's date]).

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