Is CFAP74 p.Ala704Glu (c.2111C>A) pathogenic?

CFAP74 p.Ala704Glu (c.2111C>A) is classified Uncertain significance in CFAP74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely benign (0.0918); Rare (popmax 0.756%, mid).

How common is CFAP74 p.Ala704Glu (c.2111C>A) in the general population?

CFAP74 p.Ala704Glu (c.2111C>A) is rare (popmax 0.756%, mid) (gnomAD).

What do computational predictors say about CFAP74 p.Ala704Glu (c.2111C>A)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

CFAP74 p.Ala704Glu

c.2111C>A · rs201687693 · VCV2300013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.756%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -4.96	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 -1.9	GERP -2.3
Regional constraint	o/e 1.02	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	0.074	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 0.756% Middle Eastern · 46/6,082 alleles

Filtering AF 0.583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.521%

Overall 0.0237% 382/1,614,070 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.756%	132
Ashkenazi Jewishnot grpmax-eligible	0.28%	357
Admixed American	0.0717%	1,395
Remaining individualsnot grpmax-eligible	0.0464%	2,155
South Asian	0.0143%	7,007
European (non-Finnish)	0.0138%	7,240
African / African-American	0.00667%	14,985

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.Ala704Glu
Coding: c.2111C>A
MANE Select: NM_001304360
dbSNP: rs201687693
Type: single nucleotide variant
Location: chr1:1955756 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.38
Residue 704: the 'disordered' region

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-ala704glu (accessed [today's date]).

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