Is CFP p.Arg403His (c.1208G>A) pathogenic?

CFP p.Arg403His (c.1208G>A) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-27). AlphaMissense: likely benign (0.3065); Very rare (popmax 0.00376%, sas).

How common is CFP p.Arg403His (c.1208G>A) in the general population?

CFP p.Arg403His (c.1208G>A) is very rare (popmax 0.00376%, sas) (gnomAD).

What do computational predictors say about CFP p.Arg403His (c.1208G>A)?

AlphaMissense predicts likely benign (score 0.3065) — an in-silico prediction, not a clinical call.

CFP p.Arg403His

c.1208G>A · VCV4768473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00376%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3065	likely benign
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -11.43	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	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	24.4	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 0.00376% South Asian · 2/53,237 alleles

Filtering AF 0.000623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000233%

Overall 0.00051% 6/1,176,277 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00376%	26,618
East Asian	0.00312%	32,010
Admixed American	0.00247%	40,426
European (non-Finnish)	0.000228%	438,806

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.Arg403His
Coding: c.1208G>A
MANE Select: NM_001145252
Type: single nucleotide variant
Location: chrX:47626094 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 403: a β-strand; a disulfide bond; the tsp type-1 6 domain

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

Similar variants

CFP p.Arg403Cys Uncertain significance ★ ⚠ same residue
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

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-arg403his (accessed [today's date]).

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