Is CFAP54 p.Arg319Cys (c.955C>T) pathogenic?

CFAP54 p.Arg319Cys (c.955C>T) is classified Pathogenic in CFAP54 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-11). AlphaMissense: ambiguous (0.394); Very rare (popmax 0.00548%, afr); Associated with spermatogenic failure 98.

What condition is associated with CFAP54 p.Arg319Cys (c.955C>T)?

CFAP54 p.Arg319Cys (c.955C>T) is associated with spermatogenic failure 98 (ClinVar).

How common is CFAP54 p.Arg319Cys (c.955C>T) in the general population?

CFAP54 p.Arg319Cys (c.955C>T) is very rare (popmax 0.00548%, afr) (gnomAD).

What do computational predictors say about CFAP54 p.Arg319Cys (c.955C>T)?

AlphaMissense predicts ambiguous (score 0.394) — an in-silico prediction, not a clinical call.

CFAP54 p.Arg319Cys

c.955C>T · VCV3767882

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.394 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00548%, afr)

Conditions

spermatogenic failure 98

Computational evidence

Protein change
AlphaMissense	0.394	ambiguous
REVEL	0.38	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 44 kb · p 0.46 · regional, not allelic
Overall
CADD	29.1	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 0.00548% African / African-American · 4/72,960 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000786% 12/1,526,258 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00548%	18,240
South Asian	0.0048%	20,842
Admixed American	0.00197%	50,716
European (non-Finnish)	0.000263%	379,685

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.Arg319Cys
Coding: c.955C>T
MANE Select: NM_001306084
Type: single nucleotide variant
Location: chr12:96521869 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Residue 319: 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.Arg293His 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-arg319cys (accessed [today's date]).

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