Is CFAP418 p.Glu49Gln (c.145G>C) pathogenic?

CFAP418 p.Glu49Gln (c.145G>C) is classified Uncertain significance in CFAP418 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). AlphaMissense: likely benign (0.1074); Very rare (popmax 0.000254%, nfe).

How common is CFAP418 p.Glu49Gln (c.145G>C) in the general population?

CFAP418 p.Glu49Gln (c.145G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CFAP418 p.Glu49Gln (c.145G>C)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

CFAP418 p.Glu49Gln

c.145G>C · rs775053272 · VCV2913403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.96	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 0.69	GERP -0.25, phastCons 0.16
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	12.77	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 0.000254% European (non-Finnish) · 3/1,179,960 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,768 alleles · very rare

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: CFAP418
Protein: p.Glu49Gln
Coding: c.145G>C
MANE Select: NM_177965
dbSNP: rs775053272
Type: single nucleotide variant
Location: chr8:95269045 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 49: the 'required for interaction with fam161a' region; the 'disordered' region

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

Similar variants

CFAP418 p.Glu49= Likely benign ★ 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-glu49gln (accessed [today's date]).

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