Is CFAP43 p.Val310Ala (c.929T>C) pathogenic?

CFAP43 p.Val310Ala (c.929T>C) is classified Conflicting classifications of pathogenicity in CFAP43 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-06-24). AlphaMissense: likely benign (0.1228); Rare (popmax 0.316%, mid); Associated with spermatogenic failure 19.

What condition is associated with CFAP43 p.Val310Ala (c.929T>C)?

CFAP43 p.Val310Ala (c.929T>C) is associated with spermatogenic failure 19 (ClinVar).

How common is CFAP43 p.Val310Ala (c.929T>C) in the general population?

CFAP43 p.Val310Ala (c.929T>C) is rare (popmax 0.316%, mid) (gnomAD).

What do computational predictors say about CFAP43 p.Val310Ala (c.929T>C)?

AlphaMissense predicts likely benign (score 0.1228) — an in-silico prediction, not a clinical call.

CFAP43 p.Val310Ala

c.929T>C · rs138825875 · VCV1030904

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1228 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.316%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure 19

Computational evidence

Protein change
AlphaMissense	0.1228	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.50	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 -0.47	GERP -3.2
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	4.624	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 0.316% Middle Eastern · 19/6,012 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.0219% 353/1,610,740 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.316%	316
South Asian	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.024%	4,158
European (non-Finnish)	0.0235%	4,258
Admixed American	0.0169%	5,904
Finnishnot grpmax-eligible	0.00312%	32,013
African / African-American	0.00267%	37,419

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.Val310Ala
Coding: c.929T>C
MANE Select: NM_025145
dbSNP: rs138825875
Type: single nucleotide variant
Location: chr10:104205997 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB

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 c.3541-2A>C Pathogenic same condition
CFAP43 p.Arg1118Ter Pathogenic same condition
CFAP43 p.Arg1378Ter Pathogenic same condition
CFAP43 p.Arg85Trp 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-val310ala (accessed [today's date]).

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