Is CCDC43 p.Ala9Pro (c.25G>C) pathogenic?

CCDC43 p.Ala9Pro (c.25G>C) is classified Uncertain significance in CCDC43 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely benign (0.0978); Very rare (popmax 0.00086%, nfe).

How common is CCDC43 p.Ala9Pro (c.25G>C) in the general population?

CCDC43 p.Ala9Pro (c.25G>C) is very rare (popmax 0.00086%, nfe) (gnomAD).

What do computational predictors say about CCDC43 p.Ala9Pro (c.25G>C)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

CCDC43 p.Ala9Pro

c.25G>C · rs534943447 · VCV2270608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00086%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.56	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 0.33	GERP -1.1, phastCons 0.003
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.18 · regional, not allelic
Overall
CADD	18.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00086% European (non-Finnish) · 10/1,162,720 alleles

Filtering AF 0.000435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000317%

Overall 0.000634% 10/1,576,276 alleles · very rare

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: CCDC43
Protein: p.Ala9Pro
Coding: c.25G>C
MANE Select: NM_144609
dbSNP: rs534943447
Type: single nucleotide variant
Location: chr17:44689729 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30

Full CCDC43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC43 p.Ala9Thr Uncertain significance ★ ⚠ same residue
CCDC43 p.Ala11Asp Uncertain significance ★ ⚠ same type
CCDC43 p.Ala11Ser Uncertain significance ★ ⚠ same type
CCDC43 p.Ala38Thr Uncertain significance ★ ⚠ same type
CCDC43 p.Ala42Val Uncertain significance ★ ⚠ same type
CCDC43 p.Arg177Gln Uncertain significance ★ ⚠ same type
CCDC43 p.Arg181Gln Uncertain significance ★ ⚠ same type
CCDC43 p.Arg185Trp 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/ccdc43-p-ala9pro (accessed [today's date]).

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