Is CFC1 p.Ala195Val (c.584C>T) pathogenic?

CFC1 p.Ala195Val (c.584C>T) is classified Uncertain significance in CFC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely benign (0.1042); Ultra-rare (popmax 0.0254%, amr); Associated with Inborn genetic diseases.

What condition is associated with CFC1 p.Ala195Val (c.584C>T)?

CFC1 p.Ala195Val (c.584C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFC1 p.Ala195Val (c.584C>T) in the general population?

CFC1 p.Ala195Val (c.584C>T) is ultra-rare (popmax 0.0254%, amr) (gnomAD).

What do computational predictors say about CFC1 p.Ala195Val (c.584C>T)?

AlphaMissense predicts likely benign (score 0.1042) — an in-silico prediction, not a clinical call.

CFC1 p.Ala195Val

c.584C>T · rs1401586410 · VCV2253080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1042 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1042	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.12	constrained · MANE · 6,407 bp · p 3.7e-22 · regional, not allelic
Overall
CADD	11.68	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 0.0254% Admixed American · 6/23,640 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00755%

Overall 0.00336% 17/505,618 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0254%	3,940
African / African-American	0.0177%	5,650
South Asian	0.00441%	22,692
Remaining individualsnot grpmax-eligible	0.00378%	26,484
East Asian	0.00298%	33,528
European (non-Finnish)	0.000668%	149,593

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.Ala195Val
Coding: c.584C>T
MANE Select: NM_032545
dbSNP: rs1401586410
Type: single nucleotide variant
Location: chr2:130592965 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFC1 p.Gly33Ser Uncertain significance ★★ ⚠ same condition
CFC1 p.Gly59Arg Likely benign ★★ same condition
CFC1 p.Ala79Thr Uncertain significance ★ ⚠ same condition
CFC1 p.Arg28Gly Uncertain significance ★ ⚠ same condition
CFC1 p.Arg47Leu Uncertain significance ★ ⚠ same condition
CFC1 p.Glu72Lys Uncertain significance ★ ⚠ same condition
CFC1 p.His31Arg Uncertain significance ★ ⚠ same condition
CFC1 p.Ile19Val Uncertain significance ★ ⚠ same condition

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-ala195val (accessed [today's date]).

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