Is CFAP74 p.Glu267Val (c.800A>T) pathogenic?

CFAP74 p.Glu267Val (c.800A>T) is classified Uncertain significance in CFAP74 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.2843); Ultra-rare (popmax 0.0223%, eas).

How common is CFAP74 p.Glu267Val (c.800A>T) in the general population?

CFAP74 p.Glu267Val (c.800A>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about CFAP74 p.Glu267Val (c.800A>T)?

AlphaMissense predicts likely benign (score 0.2843) — an in-silico prediction, not a clinical call.

CFAP74 p.Glu267Val

c.800A>T · rs370928445 · VCV2341887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2843	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -8.02	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 2.6	GERP 0.17, phastCons 0.25
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	19.22	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,898 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00329% 53/1,612,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0448%	2,230
East Asiangrpmax	0.0223%	4,490
Admixed American	0.0117%	8,571
South Asian	0.0022%	45,543
European (non-Finnish)	0.000509%	196,610

Remaining individuals 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.Glu267Val
Coding: c.800A>T
MANE Select: NM_001304360
dbSNP: rs370928445
Type: single nucleotide variant
Location: chr1:1972068 (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.Glu267Lys 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-glu267val (accessed [today's date]).

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