Is CCDC159 p.Tyr102Ser (c.305A>C) pathogenic?

CCDC159 p.Tyr102Ser (c.305A>C) is classified Uncertain significance in CCDC159 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: ambiguous (0.3627); Absent from gnomAD v4.1.

How common is CCDC159 p.Tyr102Ser (c.305A>C) in the general population?

CCDC159 p.Tyr102Ser (c.305A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC159 p.Tyr102Ser (c.305A>C)?

AlphaMissense predicts ambiguous (score 0.3627) — an in-silico prediction, not a clinical call.

CCDC159 p.Tyr102Ser

c.305A>C · VCV3486207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3627	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -5.05	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.55, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 8,267 bp · p 0.42 · regional, not allelic
Overall
CADD	23.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC159
Protein: p.Tyr102Ser
Coding: c.305A>C
MANE Select: NM_001080503
Type: single nucleotide variant
Location: chr19:11350886 (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-tyr102ser (accessed [today's date]).

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