Is CFAP418 p.Glu7Ala (c.20A>C) pathogenic?

CFAP418 p.Glu7Ala (c.20A>C) is classified Uncertain significance in CFAP418 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). AlphaMissense: likely benign (0.0987); Absent from gnomAD v4.1.

How common is CFAP418 p.Glu7Ala (c.20A>C) in the general population?

CFAP418 p.Glu7Ala (c.20A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP418 p.Glu7Ala (c.20A>C)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CFAP418 p.Glu7Ala

c.20A>C · rs1391298251 · VCV2021806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.57	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 5	GERP -0.89, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	15.28	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP418
Protein: p.Glu7Ala
Coding: c.20A>C
MANE Select: NM_177965
dbSNP: rs1391298251
Type: single nucleotide variant
Location: chr8:95269170 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 7: the 'required for interaction with fam161a' region

Full CFAP418 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP418 p.Glu7Ter Pathogenic ★ same residue
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same type
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same type
CFAP418 p.Trp185Ter Pathogenic/Likely pathogenic ★★ same type
CFAP418 c.*408G>A Uncertain significance ★★ same type
CFAP418 c.*965C>G Uncertain significance ★★ same type
CFAP418 p.Ala178Val Uncertain significance ★★ ⚠ same type
CFAP418 p.Ala45Gly 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/cfap418-p-glu7ala (accessed [today's date]).

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