Is CCDC181 p.Glu429Asp (c.1287A>C) pathogenic?

CCDC181 p.Glu429Asp (c.1287A>C) is classified Uncertain significance in CCDC181 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.2775); Ultra-rare (popmax 0.0813%, nfe).

How common is CCDC181 p.Glu429Asp (c.1287A>C) in the general population?

CCDC181 p.Glu429Asp (c.1287A>C) is ultra-rare (popmax 0.0813%, nfe) (gnomAD).

What do computational predictors say about CCDC181 p.Glu429Asp (c.1287A>C)?

AlphaMissense predicts likely benign (score 0.2775) — an in-silico prediction, not a clinical call.

CCDC181 p.Glu429Asp

c.1287A>C · rs143641979 · VCV2365036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2775 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2775	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -9.06	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 0.15	GERP -1.7, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.0056 · regional, not allelic
Overall
CADD	22.2	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 0.0813% European (non-Finnish) · 959/1,179,250 alleles

Filtering AF 0.077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0753%

Overall 0.063% 1,015/1,612,358 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0813%	1,230
Remaining individualsnot grpmax-eligible	0.0529%	1,891
Middle Eastern	0.0331%	3,024
Admixed American	0.0134%	7,462
African / African-American	0.0133%	7,495
East Asian	0.00447%	22,379
Finnishnot grpmax-eligible	0.00156%	63,936

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: CCDC181
Protein: p.Glu429Asp
Coding: c.1287A>C
MANE Select: NM_001300969
dbSNP: rs143641979
Type: single nucleotide variant
Location: chr1:169397320 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92

Full CCDC181 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC181 p.Ala292Thr Uncertain significance ★ ⚠ same type
CCDC181 p.Ala414Pro Uncertain significance ★ ⚠ same type
CCDC181 p.Ala41Val Uncertain significance ★ ⚠ same type
CCDC181 p.Arg150Gln Uncertain significance ★ ⚠ same type
CCDC181 p.Arg298Cys Uncertain significance ★ ⚠ same type
CCDC181 p.Arg310Gln Uncertain significance ★ ⚠ same type
CCDC181 p.Arg395Pro Uncertain significance ★ ⚠ same type
CCDC181 p.Arg416Gln 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/ccdc181-p-glu429asp (accessed [today's date]).

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