Is CFAP74 p.Pro1491= (c.4473C>T) pathogenic?

CFAP74 p.Pro1491= (c.4473C>T) is classified Benign in CFAP74 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Low-frequency (popmax 1.22%, nfe).

How common is CFAP74 p.Pro1491= (c.4473C>T) in the general population?

CFAP74 p.Pro1491= (c.4473C>T) is low-frequency (popmax 1.22%, nfe) (gnomAD).

CFAP74 p.Pro1491=

c.4473C>T · rs142831649 · VCV2638066

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -2.1
Overall
CADD	0.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.22% European (non-Finnish) · 14,287/1,174,590 alleles

Filtering AF 1.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 1.02% 16,388/1,599,954 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.71%	58
European (non-Finnish)grpmax	1.22%	82
Remaining individualsnot grpmax-eligible	1.03%	97
Admixed American	0.386%	259
African / African-American	0.169%	590
Ashkenazi Jewishnot grpmax-eligible	0.0483%	2,069
South Asian	0.0461%	2,167
East Asian	0.00225%	44,462

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: CFAP74
Protein: p.Pro1491=
Coding: c.4473C>T
MANE Select: NM_001304360
dbSNP: rs142831649
Type: single nucleotide variant
Location: chr1:1923416 (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-pro1491 (accessed [today's date]).

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