Is CFI p.Gln52His (c.156G>C) pathogenic?

CFI p.Gln52His (c.156G>C) is classified Uncertain significance in CFI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-31). AlphaMissense: ambiguous (0.5304); Very rare (popmax 8.47e-05%, nfe).

How common is CFI p.Gln52His (c.156G>C) in the general population?

CFI p.Gln52His (c.156G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CFI p.Gln52His (c.156G>C)?

AlphaMissense predicts ambiguous (score 0.5304) — an in-silico prediction, not a clinical call.

CFI p.Gln52His

c.156G>C · rs1033603086 · VCV2682869

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5304 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5304	ambiguous
REVEL	0.284	benign-leaning
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	21.4	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 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 6.84e-05% 1/1,461,880 alleles · very rare

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.Gln52His
Coding: c.156G>C
MANE Select: NM_000204
dbSNP: rs1033603086
Type: single nucleotide variant
Location: chr4:109766726 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 52: a disulfide bond; a β-strand

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

Similar variants

CFI p.Gln52= Likely benign ★ 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
CFI p.Arg474Ter 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-gln52his (accessed [today's date]).

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