Is CFP p.Ser325Arg (c.975C>A) pathogenic?

CFP p.Ser325Arg (c.975C>A) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-02). AlphaMissense: ambiguous (0.5426); Very rare (popmax 0.000447%, nfe).

How common is CFP p.Ser325Arg (c.975C>A) in the general population?

CFP p.Ser325Arg (c.975C>A) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about CFP p.Ser325Arg (c.975C>A)?

AlphaMissense predicts ambiguous (score 0.5426) — an in-silico prediction, not a clinical call.

CFP p.Ser325Arg

c.975C>A · rs756621805 · VCV2798684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5426	ambiguous
REVEL	0.217	benign-leaning
SaProt	LLR -9.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1, phastCons 0.94
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	14.86	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 0.000447% European (non-Finnish) · 4/895,444 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000364% 4/1,098,143 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: CFP
Protein: p.Ser325Arg
Coding: c.975C>A
MANE Select: NM_001145252
dbSNP: rs756621805
Type: single nucleotide variant
Location: chrX:47626485 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 325: an α-helix; the tsp type-1 5 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-ser325arg (accessed [today's date]).

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