Is CCDC43 p.Val35Met (c.103G>A) pathogenic?

CCDC43 p.Val35Met (c.103G>A) is classified Uncertain significance in CCDC43 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.2298); Rare (popmax 0.304%, afr).

How common is CCDC43 p.Val35Met (c.103G>A) in the general population?

CCDC43 p.Val35Met (c.103G>A) is rare (popmax 0.304%, afr) (gnomAD).

What do computational predictors say about CCDC43 p.Val35Met (c.103G>A)?

AlphaMissense predicts likely benign (score 0.2298) — an in-silico prediction, not a clinical call.

CCDC43 p.Val35Met

c.103G>A · VCV4221262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2298 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.304%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2298	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -8.65	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 3.2	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.18 · regional, not allelic
Overall
CADD	21.5	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 0.304% African / African-American · 228/75,062 alleles

Filtering AF 0.271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.259%

Overall 0.0202% 326/1,613,798 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.304%	329
Middle Eastern	0.116%	866
South Asian	0.0516%	1,937
Remaining individualsnot grpmax-eligible	0.04%	2,499
Admixed American	0.005%	19,993
European (non-Finnish)	0.00136%	73,739

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.Val35Met
Coding: c.103G>A
MANE Select: NM_144609
Type: single nucleotide variant
Location: chr17:44689651 (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.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.Ala9Pro Uncertain significance ★ ⚠ same type
CCDC43 p.Ala9Thr Uncertain significance ★ ⚠ same type
CCDC43 p.Arg177Gln Uncertain significance ★ ⚠ same type
CCDC43 p.Arg181Gln 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-val35met (accessed [today's date]).

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