Is CFI p.Trp51Arg (c.151T>C) pathogenic?

CFI p.Trp51Arg (c.151T>C) is classified Uncertain significance in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). AlphaMissense: likely pathogenic (0.9883); Very rare (popmax 0.00768%, sas).

How common is CFI p.Trp51Arg (c.151T>C) in the general population?

CFI p.Trp51Arg (c.151T>C) is very rare (popmax 0.00768%, sas) (gnomAD).

What do computational predictors say about CFI p.Trp51Arg (c.151T>C)?

AlphaMissense predicts likely pathogenic (score 0.9883) — an in-silico prediction, not a clinical call.

CFI p.Trp51Arg

c.151T>C · rs764739067 · VCV2990335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9883	likely pathogenic · top 4% in CFI
REVEL	0.714	pathogenic-leaning
SaProt	LLR -15.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00768% South Asian · 7/91,092 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000991% 16/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0064%	15,623
Admixed American	0.00333%	30,004
European (non-Finnish)	0.000254%	393,345

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: CFI
Protein: p.Trp51Arg
Coding: c.151T>C
MANE Select: NM_000204
dbSNP: rs764739067
Type: single nucleotide variant
Location: chr4:109766731 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 51: a disulfide bond

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

Similar variants

CFI p.Trp51Cys Uncertain significance ★★ ⚠ same residue
CFI p.Trp51Ser Uncertain significance ★★ ⚠ same residue
CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same type
CFI c.57+1G>C Likely pathogenic ★★ same type
CFI c.658+1G>A Likely pathogenic ★★ same type
CFI c.905-1G>C Likely pathogenic ★★ same type
CFI p.Ala258Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
CFI p.Arg187Ter Pathogenic/Likely pathogenic ★★ 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/cfi-p-trp51arg (accessed [today's date]).

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