Is CASTOR1 p.Pro272Ser (c.814C>T) pathogenic?

CASTOR1 p.Pro272Ser (c.814C>T) is classified Uncertain significance in CASTOR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: likely pathogenic (0.7822); Very rare (popmax 0.00134%, afr).

How common is CASTOR1 p.Pro272Ser (c.814C>T) in the general population?

CASTOR1 p.Pro272Ser (c.814C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CASTOR1 p.Pro272Ser (c.814C>T)?

AlphaMissense predicts likely pathogenic (score 0.7822) — an in-silico prediction, not a clinical call.

CASTOR1 p.Pro272Ser

c.814C>T · rs1301568715 · VCV2604911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7822	likely pathogenic
REVEL	0.387	indeterminate
SaProt	LLR -9.13	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 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 3,874 bp · p 6.6e-05 · regional, not allelic
Overall
CADD	29.2	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 0.00134% African / African-American · 1/74,792 alleles

Overall 0.000657% 1/152,242 alleles · very rare

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: CASTOR1
Protein: p.Pro272Ser
Coding: c.814C>T
MANE Select: NM_001037666
dbSNP: rs1301568715
Type: single nucleotide variant
Location: chr22:30286028 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.84 · 11 PDB
Residue 272: the act 2 domain

Full CASTOR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASTOR1 c.505+2T>C Uncertain significance ★ same type
CASTOR1 p.Ala196Thr Uncertain significance ★ ⚠ same type
CASTOR1 p.Ala198Thr Uncertain significance ★ ⚠ same type
CASTOR1 p.Ala87Val Uncertain significance ★ ⚠ same type
CASTOR1 p.Ala92Thr Uncertain significance ★ ⚠ same type
CASTOR1 p.Ala98Thr Uncertain significance ★ ⚠ same type
CASTOR1 p.Arg145Cys Uncertain significance ★ ⚠ same type
CASTOR1 p.Arg267His 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/castor1-p-pro272ser (accessed [today's date]).

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