Is CFC1 p.Trp68Cys (c.204G>T) pathogenic?

CFC1 p.Trp68Cys (c.204G>T) is classified Uncertain significance in CFC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-06). AlphaMissense: likely pathogenic (0.6553); Very rare (popmax 0.00271%, nfe).

How common is CFC1 p.Trp68Cys (c.204G>T) in the general population?

CFC1 p.Trp68Cys (c.204G>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about CFC1 p.Trp68Cys (c.204G>T)?

AlphaMissense predicts likely pathogenic (score 0.6553) — an in-silico prediction, not a clinical call.

CFC1 p.Trp68Cys

c.204G>T · rs371700198 · VCV420508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6553	likely pathogenic
REVEL	0.376	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	phastCons 0.99
Regional constraint	o/e 0.12	constrained · MANE · 6,407 bp · p 3.7e-22 · regional, not allelic
Overall
CADD	22.8	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 0.00271% European (non-Finnish) · 32/1,179,866 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00198% 32/1,613,820 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: CFC1
Protein: p.Trp68Cys
Coding: c.204G>T
MANE Select: NM_032545
dbSNP: rs371700198
Type: single nucleotide variant
Location: chr2:130598685 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.86 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.18

Full CFC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFC1 p.Gly33Ser Uncertain significance ★★ ⚠ same type
CFC1 p.Ala145Thr Benign ★★ same type
CFC1 p.Arg47Gln Benign ★★ same type
CFC1 p.Asn21= Benign/Likely benign ★★ same type
CFC1 p.Asn21His Benign ★★ same type
CFC1 p.Gly59Arg Likely benign ★★ same type
CFC1 p.Leu202= Benign/Likely benign ★★ same type
CFC1 p.Ala195Val 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/cfc1-p-trp68cys (accessed [today's date]).

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