Is CFAP54 p.Arg1629Cys (c.4885C>T) pathogenic?

CFAP54 p.Arg1629Cys (c.4885C>T) is classified Pathogenic in CFAP54 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely pathogenic (0.6676); Very rare (popmax 0.00223%, eas); Associated with spermatogenic failure 98.

What condition is associated with CFAP54 p.Arg1629Cys (c.4885C>T)?

CFAP54 p.Arg1629Cys (c.4885C>T) is associated with spermatogenic failure 98 (ClinVar).

How common is CFAP54 p.Arg1629Cys (c.4885C>T) in the general population?

CFAP54 p.Arg1629Cys (c.4885C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CFAP54 p.Arg1629Cys (c.4885C>T)?

AlphaMissense predicts likely pathogenic (score 0.6676) — an in-silico prediction, not a clinical call.

CFAP54 p.Arg1629Cys

c.4885C>T · VCV3767884

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

spermatogenic failure 98

Computational evidence

Protein change
AlphaMissense	0.6676	likely pathogenic ✓ concordant with ClinVar
REVEL	0.513	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 327 kb · p 0.17 · regional, not allelic
Overall
CADD	29.3	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 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00123% 18/1,461,666 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,830
East Asiangrpmax	0.00223%	44,874
Admixed American	0.00167%	60,006
European (non-Finnish)	0.0011%	90,761

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1629Cys
Coding: c.4885C>T
MANE Select: NM_001306084
Type: single nucleotide variant
Location: chr12:96651600 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Residue 1629: 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.Arg293His 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-arg1629cys (accessed [today's date]).

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