Is CFP p.Pro289Ser (c.865C>T) pathogenic?

CFP p.Pro289Ser (c.865C>T) is classified Likely benign in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). AlphaMissense: likely benign (0.3287); Ultra-rare (popmax 0.062%, sas).

How common is CFP p.Pro289Ser (c.865C>T) in the general population?

CFP p.Pro289Ser (c.865C>T) is ultra-rare (popmax 0.062%, sas) (gnomAD).

What do computational predictors say about CFP p.Pro289Ser (c.865C>T)?

AlphaMissense predicts likely benign (score 0.3287) — an in-silico prediction, not a clinical call.

CFP p.Pro289Ser

c.865C>T · rs766160459 · VCV2168803

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3287 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.062%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3287	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense 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 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	22.9	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 0.062% South Asian · 35/56,472 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0402%

Overall 0.00306% 37/1,209,405 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.062%	1,613
Remaining individualsnot grpmax-eligible	0.00421%	23,766

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: CFP
Protein: p.Pro289Ser
Coding: c.865C>T
MANE Select: NM_001145252
dbSNP: rs766160459
Type: single nucleotide variant
Location: chrX:47626848 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 289: a disulfide bond; the tsp type-1 4 domain

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

Similar variants

CFP p.Trp321Gly Pathogenic ★★ same type
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same type
CFP p.Arg157Gln Uncertain significance ★★ ⚠ same type
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same type
CFP p.Arg159Cys Uncertain significance ★★ ⚠ same type
CFP p.Arg247Trp Uncertain significance ★★ ⚠ same type
CFP p.Arg438Trp Uncertain significance ★★ ⚠ same type
CFP p.Asn307Ser 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/cfp-p-pro289ser (accessed [today's date]).

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