Is CFAP74 p.Arg513Cys (c.1537C>T) pathogenic?

CFAP74 p.Arg513Cys (c.1537C>T) is classified Likely benign in CFAP74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-14). AlphaMissense: likely benign (0.0794); Ultra-rare (popmax 0.0379%, eas).

How common is CFAP74 p.Arg513Cys (c.1537C>T) in the general population?

CFAP74 p.Arg513Cys (c.1537C>T) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about CFAP74 p.Arg513Cys (c.1537C>T)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

CFAP74 p.Arg513Cys

c.1537C>T · rs766114699 · VCV2292160

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -3.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.027	GERP -2.6
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	13.93	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 0.0379% East Asian · 17/44,874 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.0026% 42/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	0.00195%	51,302

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.Arg513Cys
Coding: c.1537C>T
MANE Select: NM_001304360
dbSNP: rs766114699
Type: single nucleotide variant
Location: chr1:1964926 (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.Arg513His Uncertain significance ★ ⚠ same residue
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-arg513cys (accessed [today's date]).

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