Is CFC1 p.Arg47Gln (c.140G>A) pathogenic?

CFC1 p.Arg47Gln (c.140G>A) is classified Benign in CFC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2013-08-07). AlphaMissense: likely benign (0.0581); Common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CFC1 p.Arg47Gln (c.140G>A)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

CFC1 p.Arg47Gln

Q: How common is CFC1 p.Arg47Gln (c.140G>A) in the general population?

CFC1 p.Arg47Gln (c.140G>A) is common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.140G>A · rs201431919 · VCV136733

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.05	phastCons 0.003
Regional constraint	o/e 0.12	constrained · MANE · 6,407 bp · p 3.7e-22 · regional, not allelic
Overall
CADD	6.04	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 19.6% African / African-American · 13,188/67,336 alleles

Filtering AF 19.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.2%

Overall 0.98% 15,721/1,604,432 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.6%	5
Remaining individualsnot grpmax-eligible	1.46%	68
Admixed American	1.43%	70
Middle Eastern	1.1%	91
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
European (non-Finnish)	0.0536%	1,866
South Asian	0.0483%	2,069
Finnishnot grpmax-eligible	0.0125%	8,001

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.Arg47Gln
Coding: c.140G>A
MANE Select: NM_032545
dbSNP: rs201431919
Type: single nucleotide variant
Location: chr2:130598749 (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.Arg47Leu Uncertain significance ★ ⚠ same residue
CFC1 p.Gly33Ser Uncertain significance ★★ ⚠ same type
CFC1 p.Ala145Thr 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-arg47gln (accessed [today's date]).

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