Is CCDC158 p.Ser288Asn (c.863G>A) pathogenic?

CCDC158 p.Ser288Asn (c.863G>A) is classified Uncertain significance in CCDC158 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0918); Very rare (popmax 0.000932%, nfe).

How common is CCDC158 p.Ser288Asn (c.863G>A) in the general population?

CCDC158 p.Ser288Asn (c.863G>A) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about CCDC158 p.Ser288Asn (c.863G>A)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

CCDC158 p.Ser288Asn

c.863G>A · VCV4649220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.69	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 2.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 90 kb · p 0.26 · regional, not allelic
Overall
CADD	16.25	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 0.000932% European (non-Finnish) · 11/1,179,776 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,580 alleles · very rare

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: CCDC158
Protein: p.Ser288Asn
Coding: c.863G>A
MANE Select: NM_001394954
Type: single nucleotide variant
Location: chr4:76382661 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.43

Full CCDC158 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC158 p.Ala1046Pro Uncertain significance ★ ⚠ same type
CCDC158 p.Ala336Ser Uncertain significance ★ ⚠ same type
CCDC158 p.Ala451Thr Uncertain significance ★ ⚠ same type
CCDC158 p.Ala452Ser Uncertain significance ★ ⚠ same type
CCDC158 p.Ala468Asp Uncertain significance ★ ⚠ same type
CCDC158 p.Ala618Thr Uncertain significance ★ ⚠ same type
CCDC158 p.Ala704Thr Uncertain significance ★ ⚠ same type
CCDC158 p.Ala704Val 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/ccdc158-p-ser288asn (accessed [today's date]).

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