Is CCDC159 p.Glu51Lys (c.151G>A) pathogenic?

CCDC159 p.Glu51Lys (c.151G>A) is classified Uncertain significance in CCDC159 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely pathogenic (0.7265); Very rare (popmax 0.00549%, sas).

How common is CCDC159 p.Glu51Lys (c.151G>A) in the general population?

CCDC159 p.Glu51Lys (c.151G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about CCDC159 p.Glu51Lys (c.151G>A)?

AlphaMissense predicts likely pathogenic (score 0.7265) — an in-silico prediction, not a clinical call.

CCDC159 p.Glu51Lys

c.151G>A · VCV4220779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7265 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7265	likely pathogenic
REVEL	0.165	moderately benign-leaning
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,267 bp · p 0.42 · regional, not allelic
Overall
CADD	29.1	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 0.00549% South Asian · 5/91,022 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00136% 22/1,613,326 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,204
East Asian	0.00446%	22,428
Admixed American	0.00167%	59,908
Remaining individualsnot grpmax-eligible	0.0016%	62,456
African / African-American	0.00134%	74,814
European (non-Finnish)	0.00102%	98,313

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.Glu51Lys
Coding: c.151G>A
MANE Select: NM_001080503
Type: single nucleotide variant
Location: chr19:11350124 (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.Ala45Asp 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

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-glu51lys (accessed [today's date]).

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