Is CFP p.Thr400Ala (c.1198A>G) pathogenic?

CFP p.Thr400Ala (c.1198A>G) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). AlphaMissense: likely benign (0.0787); Very rare (popmax 0.00388%, nfe).

How common is CFP p.Thr400Ala (c.1198A>G) in the general population?

CFP p.Thr400Ala (c.1198A>G) is very rare (popmax 0.00388%, nfe) (gnomAD).

What do computational predictors say about CFP p.Thr400Ala (c.1198A>G)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

CFP p.Thr400Ala

c.1198A>G · rs373037904 · VCV1980446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00388%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -9.04	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 -0.15	GERP 0.67
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	8.6	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 0.00388% European (non-Finnish) · 34/876,850 alleles

Filtering AF 0.00279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00307% 36/1,174,456 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00432%	23,123
European (non-Finnish)grpmax	0.00388%	25,790

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr400Ala
Coding: c.1198A>G
MANE Select: NM_001145252
dbSNP: rs373037904
Type: single nucleotide variant
Location: chrX:47626104 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 400: 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.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-thr400ala (accessed [today's date]).

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