Is CFAP43 p.Val347Ala (c.1040T>C) pathogenic?

CFAP43 p.Val347Ala (c.1040T>C) is classified Pathogenic in CFAP43 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-05-02). AlphaMissense: likely benign (0.2799); Ultra-rare (popmax 0.0318%, nfe); Associated with spermatogenic failure 19.

What condition is associated with CFAP43 p.Val347Ala (c.1040T>C)?

CFAP43 p.Val347Ala (c.1040T>C) is associated with spermatogenic failure 19 (ClinVar).

How common is CFAP43 p.Val347Ala (c.1040T>C) in the general population?

CFAP43 p.Val347Ala (c.1040T>C) is ultra-rare (popmax 0.0318%, nfe) (gnomAD).

What do computational predictors say about CFAP43 p.Val347Ala (c.1040T>C)?

AlphaMissense predicts likely benign (score 0.2799) — an in-silico prediction, not a clinical call.

CFAP43 p.Val347Ala

c.1040T>C · rs147356105 · VCV523149

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2799 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure 19

Computational evidence

Protein change
AlphaMissense	0.2799	likely benign ⚠ discordant with ClinVar
REVEL	0.262	benign-leaning
SaProt	LLR -6.26	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 9.2	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	16.8	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 0.0318% European (non-Finnish) · 375/1,178,940 alleles

Filtering AF 0.0291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.0245% 395/1,611,596 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0318%	3,144
Remaining individualsnot grpmax-eligible	0.0144%	6,935
African / African-American	0.00935%	10,701
Finnishnot grpmax-eligible	0.00313%	31,957
Admixed American	0.00167%	59,756
South Asian	0.00111%	90,260

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: CFAP43
Protein: p.Val347Ala
Coding: c.1040T>C
MANE Select: NM_025145
dbSNP: rs147356105
Type: single nucleotide variant
Location: chr10:104203727 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB
Residue 347: 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-val347ala (accessed [today's date]).

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