Is CFP p.Arg438Gln (c.1313G>A) pathogenic?

CFP p.Arg438Gln (c.1313G>A) is classified Conflicting classifications of pathogenicity in CFP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-30). AlphaMissense: likely benign (0.068); Ultra-rare (popmax 0.011%, amr); Associated with Inborn genetic diseases.

What condition is associated with CFP p.Arg438Gln (c.1313G>A)?

CFP p.Arg438Gln (c.1313G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFP p.Arg438Gln (c.1313G>A) in the general population?

CFP p.Arg438Gln (c.1313G>A) is ultra-rare (popmax 0.011%, amr) (gnomAD).

What do computational predictors say about CFP p.Arg438Gln (c.1313G>A)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

CFP p.Arg438Gln

c.1313G>A · rs762270639 · VCV2723390

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -3.68	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 -5.3	GERP -3.5
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	0.002	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 0.011% Admixed American · 5/45,404 alleles

Filtering AF 0.00431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00273%

Overall 0.000663% 8/1,207,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.011%	9,081
African / African-American	0.00178%	56,255
European (non-Finnish)	0.000224%	447,189

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.Arg438Gln
Coding: c.1313G>A
MANE Select: NM_001145252
dbSNP: rs762270639
Type: single nucleotide variant
Location: chrX:47624372 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 438: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFP p.Arg438Trp Uncertain significance ★★ ⚠ same residue
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same condition
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CFP p.Asn307Ser Uncertain significance ★★ ⚠ same condition
CFP p.Glu215Lys Uncertain significance ★★ ⚠ same condition
CFP p.Gly200Asp Uncertain significance ★★ ⚠ same condition
CFP p.Lys413Glu Uncertain significance ★★ ⚠ same condition
CFP p.Phe431Val Uncertain significance ★★ ⚠ same condition

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-arg438gln (accessed [today's date]).

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