Is CFP p.Lys413Glu (c.1237A>G) pathogenic?

CFP p.Lys413Glu (c.1237A>G) is classified Uncertain significance in CFP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-23). AlphaMissense: likely benign (0.0925); Very rare (popmax 0.00743%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFP p.Lys413Glu (c.1237A>G)?

CFP p.Lys413Glu (c.1237A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFP p.Lys413Glu (c.1237A>G) in the general population?

CFP p.Lys413Glu (c.1237A>G) is very rare (popmax 0.00743%, nfe) (gnomAD).

What do computational predictors say about CFP p.Lys413Glu (c.1237A>G)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

CFP p.Lys413Glu

c.1237A>G · rs1421421234 · VCV2554793

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00743%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -4.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	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	19.41	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 0.00743% European (non-Finnish) · 65/875,182 alleles

Filtering AF 0.00597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00544%

Overall 0.00632% 67/1,060,890 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00743%	13,464
Remaining individualsnot grpmax-eligible	0.00433%	23,098

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.Lys413Glu
Coding: c.1237A>G
MANE Select: NM_001145252
dbSNP: rs1421421234
Type: single nucleotide variant
Location: chrX:47626065 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 413: 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.Ala402Gly Uncertain significance ★★ ⚠ same condition
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CFP p.Arg438Trp 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.Phe431Val Uncertain significance ★★ ⚠ same condition
CFP p.Pro204Arg 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-lys413glu (accessed [today's date]).

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