Is CFAP74 p.Glu152Lys (c.454G>A) pathogenic?

CFAP74 p.Glu152Lys (c.454G>A) is classified Uncertain significance in CFAP74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: ambiguous (0.3695); Very rare (popmax 0.00223%, eas).

How common is CFAP74 p.Glu152Lys (c.454G>A) in the general population?

CFAP74 p.Glu152Lys (c.454G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CFAP74 p.Glu152Lys (c.454G>A)?

AlphaMissense predicts ambiguous (score 0.3695) — an in-silico prediction, not a clinical call.

CFAP74 p.Glu152Lys

c.454G>A · rs1019225917 · VCV2278968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.3695	ambiguous
REVEL	0.325	indeterminate
SaProt	LLR -9.06	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	22.5	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 0.00223% East Asian · 1/44,886 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000929% 15/1,614,118 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,251
East Asiangrpmax	0.00223%	44,886
South Asian	0.0022%	45,543
African / African-American	0.00133%	75,076
European (non-Finnish)	0.000763%	131,115

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.Glu152Lys
Coding: c.454G>A
MANE Select: NM_001304360
dbSNP: rs1019225917
Type: single nucleotide variant
Location: chr1:1985432 (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-glu152lys (accessed [today's date]).

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