Is CFAP74 p.Arg307Cys (c.919C>T) pathogenic?

CFAP74 p.Arg307Cys (c.919C>T) is classified Likely benign in CFAP74 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.1309); Low-frequency (popmax 1.36%, afr).

How common is CFAP74 p.Arg307Cys (c.919C>T) in the general population?

CFAP74 p.Arg307Cys (c.919C>T) is low-frequency (popmax 1.36%, afr) (gnomAD).

What do computational predictors say about CFAP74 p.Arg307Cys (c.919C>T)?

AlphaMissense predicts likely benign (score 0.1309) — an in-silico prediction, not a clinical call.

CFAP74 p.Arg307Cys

c.919C>T · VCV4084040

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1309 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.36%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1309	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -10.23	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 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	24.3	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 1.36% African / African-American · 1,017/75,054 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 0.106% 1,711/1,614,130 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.36%	74
Remaining individualsnot grpmax-eligible	0.096%	1,042
Admixed American	0.0766%	1,305
European (non-Finnish)	0.0476%	2,100
South Asian	0.0231%	4,338
Middle Eastern	0.0165%	6,062
Finnishnot grpmax-eligible	0.00469%	21,331
East Asian	0.00223%	44,888

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.Arg307Cys
Coding: c.919C>T
MANE Select: NM_001304360
Type: single nucleotide variant
Location: chr1:1970786 (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

Similar variants

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
CFAP74 c.785+1G>A 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-arg307cys (accessed [today's date]).

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