Is CFAP54 p.Arg293His (c.878G>A) pathogenic?

CFAP54 p.Arg293His (c.878G>A) is classified Pathogenic in CFAP54 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-11). AlphaMissense: ambiguous (0.5089); Ultra-rare (popmax 0.0219%, afr); Associated with spermatogenic failure 98.

What condition is associated with CFAP54 p.Arg293His (c.878G>A)?

CFAP54 p.Arg293His (c.878G>A) is associated with spermatogenic failure 98 (ClinVar).

How common is CFAP54 p.Arg293His (c.878G>A) in the general population?

CFAP54 p.Arg293His (c.878G>A) is ultra-rare (popmax 0.0219%, afr) (gnomAD).

What do computational predictors say about CFAP54 p.Arg293His (c.878G>A)?

AlphaMissense predicts ambiguous (score 0.5089) — an in-silico prediction, not a clinical call.

CFAP54 p.Arg293His

c.878G>A · VCV3767881

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5089 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0219%, afr)

Conditions

spermatogenic failure 98

Computational evidence

Protein change
AlphaMissense	0.5089	ambiguous
REVEL	0.31	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 44 kb · p 0.46 · regional, not allelic
Overall
CADD	25.8	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 0.0219% African / African-American · 16/72,996 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00938% 144/1,535,802 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0219%	4,562
European (non-Finnish)	0.01%	9,973
Remaining individualsnot grpmax-eligible	0.01%	9,998
East Asian	0.00977%	10,231
Admixed American	0.00393%	25,477
Finnishnot grpmax-eligible	0.00225%	44,484

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: CFAP54
Protein: p.Arg293His
Coding: c.878G>A
MANE Select: NM_001306084
Type: single nucleotide variant
Location: chr12:96519007 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Residue 293: a UniProt-annotated variant site (in spgf98; uncertain significance)

Full CFAP54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 98 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP54 p.Gln649Ter Likely pathogenic ★ same condition
CFAP54 p.Arg1629Cys Pathogenic same condition
CFAP54 p.Arg319Cys Pathogenic same condition
CFAP54 p.Gly313Arg Pathogenic same condition
CFAP54 p.Leu2882fs Likely pathogenic ★ same condition
CFAP54 p.Phe1106fs Pathogenic same condition
CFAP54 p.Pro22= Likely benign ★★ same type
CFAP54 p.Arg915Gln 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/cfap54-p-arg293his (accessed [today's date]).

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