Is CFD p.Gln119His (c.357G>T) pathogenic?

CFD p.Gln119His (c.357G>T) is classified Uncertain significance in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely pathogenic (0.5851); Absent from gnomAD v4.1.

How common is CFD p.Gln119His (c.357G>T) in the general population?

CFD p.Gln119His (c.357G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFD p.Gln119His (c.357G>T)?

AlphaMissense predicts likely pathogenic (score 0.5851) — an in-silico prediction, not a clinical call.

CFD p.Gln119His

c.357G>T · rs773957525 · VCV1375721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5851 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,830)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5851	likely pathogenic
REVEL	0.505	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.94	donor loss · deltas
Pangolin	Δ0.78	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,597,830). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFD
Protein: p.Gln119His
Coding: c.357G>T
MANE Select: NM_001928
dbSNP: rs773957525
Type: single nucleotide variant
Location: chr19:861005 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.19 · 40 PDB
Residue 119: the peptidase s1 domain; a β-strand

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

Similar variants

CFD c.212+2T>G Likely pathogenic ★★ same type
CFD c.56-1G>C Likely pathogenic ★★ same type
CFD p.Tyr95Ter Pathogenic ★★ same type
ELANE p.Gly203Arg Pathogenic ★★ same type
ELANE p.Ser126Leu Pathogenic ★★ ⚠ same type
CFD p.Ala100Pro Uncertain significance ★★ same type
CFD p.Ala129Thr Uncertain significance ★★ ⚠ same type
CFD p.Ala143Val 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/cfd-p-gln119his (accessed [today's date]).

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