Is CCDC159 p.Ala45Asp (c.134C>A) pathogenic?

CCDC159 p.Ala45Asp (c.134C>A) is classified Uncertain significance in CCDC159 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-15). AlphaMissense: likely pathogenic (0.7885); Ultra-rare (popmax 0.0178%, eas).

How common is CCDC159 p.Ala45Asp (c.134C>A) in the general population?

CCDC159 p.Ala45Asp (c.134C>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CCDC159 p.Ala45Asp (c.134C>A)?

AlphaMissense predicts likely pathogenic (score 0.7885) — an in-silico prediction, not a clinical call.

CCDC159 p.Ala45Asp

c.134C>A · rs767361219 · VCV2359073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7885	likely pathogenic · top 9% in CCDC159
REVEL	0.171	moderately benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,267 bp · p 0.42 · regional, not allelic
Overall
CADD	27.4	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 0.0178% East Asian · 8/44,862 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000992% 16/1,613,704 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,608
South Asian	0.00549%	18,215
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	8.48e-05%	1,179,786

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: CCDC159
Protein: p.Ala45Asp
Coding: c.134C>A
MANE Select: NM_001080503
dbSNP: rs767361219
Type: single nucleotide variant
Location: chr19:11350016 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.97

Full CCDC159 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC159 p.Ala203Thr Uncertain significance ★ ⚠ same type
CCDC159 p.Arg117Cys Uncertain significance ★ ⚠ same type
CCDC159 p.Arg117His Uncertain significance ★ ⚠ same type
CCDC159 p.Arg124Trp Uncertain significance ★ ⚠ same type
CCDC159 p.Arg126Gly Uncertain significance ★ ⚠ same type
CCDC159 p.Arg139Gln Uncertain significance ★ ⚠ same type
CCDC159 p.Arg139Trp Uncertain significance ★ ⚠ same type
CCDC159 p.Arg153Gln 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/ccdc159-p-ala45asp (accessed [today's date]).

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