Is CFP p.Arg67His (c.200G>A) pathogenic?

CFP p.Arg67His (c.200G>A) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.066); Ultra-rare (popmax 0.0135%, amr).

How common is CFP p.Arg67His (c.200G>A) in the general population?

CFP p.Arg67His (c.200G>A) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about CFP p.Arg67His (c.200G>A)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

CFP p.Arg67His

c.200G>A · rs370592348 · VCV1406636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -3.2
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	2.039	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0135% Admixed American · 5/37,028 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00336%

Overall 0.00179% 20/1,115,797 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0135%	7,406
Remaining individualsnot grpmax-eligible	0.00235%	42,620
South Asian	0.00193%	51,947
European (non-Finnish)	0.00155%	64,665

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.Arg67His
Coding: c.200G>A
MANE Select: NM_001145252
dbSNP: rs370592348
Type: single nucleotide variant
Location: chrX:47629551 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 67: the tsp type-1 0 domain; a disulfide bond; a β-strand

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-arg67his (accessed [today's date]).

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