Is CFAP47 p.Cys440Arg (c.1318T>C) pathogenic?

CFAP47 p.Cys440Arg (c.1318T>C) is classified Likely benign in CFAP47 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.7806); Ultra-rare (popmax 0.0145%, nfe).

How common is CFAP47 p.Cys440Arg (c.1318T>C) in the general population?

CFAP47 p.Cys440Arg (c.1318T>C) is ultra-rare (popmax 0.0145%, nfe) (gnomAD).

What do computational predictors say about CFAP47 p.Cys440Arg (c.1318T>C)?

AlphaMissense predicts likely pathogenic (score 0.7806) — an in-silico prediction, not a clinical call.

CFAP47 p.Cys440Arg

c.1318T>C · rs150580241 · VCV3024988

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.7806	likely pathogenic · top 8% in CFAP47
REVEL	0.14	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 465 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	19.45	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 0.0145% European (non-Finnish) · 130/895,034 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0122% 147/1,209,659 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0258%	3,882
European (non-Finnish)grpmax	0.0145%	6,885
Remaining individualsnot grpmax-eligible	0.0063%	15,863
East Asian	0.00296%	33,732
African / African-American	0.00175%	57,123

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP47
Protein: p.Cys440Arg
Coding: c.1318T>C
MANE Select: NM_001304548
dbSNP: rs150580241
Type: single nucleotide variant
Location: chrX:35956104 (GRCh38)

Full CFAP47 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP47 p.Ser964Gly Uncertain significance ★★ same type
CFAP47 p.Thr2847Met Likely benign ★★ same type
CFAP47 c.3652-4G>C Uncertain significance ★ same type
CFAP47 p.Ala566Ser Uncertain significance ★ ⚠ same type
CFAP47 p.Arg429Cys Uncertain significance ★ ⚠ same type
CFAP47 p.Asp1565Val Uncertain significance ★ ⚠ same type
CFAP47 p.Gln2891His Uncertain significance ★ ⚠ same type
CFAP47 p.Gln439Pro 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/cfap47-p-cys440arg (accessed [today's date]).

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