Is CFAP43 p.Ser129Tyr (c.386C>A) pathogenic?

CFAP43 p.Ser129Tyr (c.386C>A) is classified Pathogenic in CFAP43 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-07-25). AlphaMissense: likely pathogenic (0.937); Absent from gnomAD v4.1; Associated with spermatogenic failure 19.

What condition is associated with CFAP43 p.Ser129Tyr (c.386C>A)?

CFAP43 p.Ser129Tyr (c.386C>A) is associated with spermatogenic failure 19 (ClinVar).

How common is CFAP43 p.Ser129Tyr (c.386C>A) in the general population?

CFAP43 p.Ser129Tyr (c.386C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP43 p.Ser129Tyr (c.386C>A)?

AlphaMissense predicts likely pathogenic (score 0.937) — an in-silico prediction, not a clinical call.

CFAP43 p.Ser129Tyr

c.386C>A · rs1131692266 · VCV430935

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

spermatogenic failure 19

Computational evidence

Protein change
AlphaMissense	0.937	likely pathogenic ✓ concordant with ClinVar · top 3% in CFAP43
REVEL	0.589	indeterminate
SaProt	LLR -14.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	28.9	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

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: CFAP43
Protein: p.Ser129Tyr
Coding: c.386C>A
MANE Select: NM_025145
dbSNP: rs1131692266
Type: single nucleotide variant
Location: chr10:104225491 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB
Residue 129: a UniProt-annotated variant site (in spgf19; uncertain significance)

Full CFAP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 19 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP43 p.Arg894Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP43 p.Arg1049Ter Likely pathogenic ★ same condition
CFAP43 p.Glu920Ter Likely pathogenic ★ same condition
CFAP43 p.Trp141Arg Uncertain significance ★ ⚠ same condition
CFAP43 p.Val310Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
CFAP43 c.3541-2A>C Pathogenic same condition
CFAP43 p.Arg1118Ter Pathogenic same condition
CFAP43 p.Arg1378Ter Pathogenic same condition

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/cfap43-p-ser129tyr (accessed [today's date]).

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