Is CFAP74 p.Arg818Trp (c.2452C>T) pathogenic?

CFAP74 p.Arg818Trp (c.2452C>T) is classified Likely pathogenic in CFAP74 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.2828); Ultra-rare (popmax 0.0507%, afr); Associated with CFAP74-related disorder.

What condition is associated with CFAP74 p.Arg818Trp (c.2452C>T)?

CFAP74 p.Arg818Trp (c.2452C>T) is associated with CFAP74-related disorder (ClinVar).

How common is CFAP74 p.Arg818Trp (c.2452C>T) in the general population?

CFAP74 p.Arg818Trp (c.2452C>T) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

What do computational predictors say about CFAP74 p.Arg818Trp (c.2452C>T)?

AlphaMissense predicts likely benign (score 0.2828) — an in-silico prediction, not a clinical call.

CFAP74 p.Arg818Trp

c.2452C>T · VCV3362882

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2828 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFAP74-related disorder

Computational evidence

Protein change
AlphaMissense	0.2828	likely benign ⚠ discordant with ClinVar
REVEL	0.152	moderately benign-leaning
SaProt	LLR -13.81	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.53, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0507% African / African-American · 37/73,032 alleles

Filtering AF 0.0378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0333%

Overall 0.0118% 182/1,535,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,974
East Asian	0.0415%	2,408
Remaining individualsnot grpmax-eligible	0.015%	6,664
Admixed American	0.00981%	10,196
European (non-Finnish)	0.0095%	10,522
South Asian	0.00595%	16,811

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: CFAP74
Protein: p.Arg818Trp
Coding: c.2452C>T
MANE Select: NM_001304360
Type: single nucleotide variant
Location: chr1:1944365 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.38

Full CFAP74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CFAP74-related disorder

Similar variants

CFAP74 p.Val1015Ala Likely pathogenic ⚠ same condition
CFAP74 p.Lys394Met Uncertain significance ★★ ⚠ same type
CFAP74 p.Arg365Gln Likely benign ★★ same type
CFAP74 p.Gly5Ser Likely benign ★★ same type
CFAP74 p.Arg280Ter Likely pathogenic ★ same type
CFAP74 c.1851+2T>C Uncertain significance ★ same type
CFAP74 c.2176+30T>G Uncertain significance ★ same type
CFAP74 c.2176+34C>T 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/cfap74-p-arg818trp (accessed [today's date]).

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