Is CCDC154 p.Lys230Gln (c.688A>C) pathogenic?

CCDC154 p.Lys230Gln (c.688A>C) is classified Uncertain significance in CCDC154 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Very rare (popmax 8.72e-05%, nfe).

How common is CCDC154 p.Lys230Gln (c.688A>C) in the general population?

CCDC154 p.Lys230Gln (c.688A>C) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

CCDC154 p.Lys230Gln

c.688A>C · VCV3996624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.051	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.23, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,911 bp · p 0.42 · regional, not allelic
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,844 alleles

Overall 7.15e-05% 1/1,397,808 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: CCDC154
Protein: p.Lys230Gln
Coding: c.688A>C
MANE Select: NM_001143980
Type: single nucleotide variant
Location: chr16:1439114 (GRCh38)
Gene constraint: LOEUF 1.366 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.92

Full CCDC154 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC154 p.Ala128Val Uncertain significance ★ same type
CCDC154 p.Ala129Gly Uncertain significance ★ same type
CCDC154 p.Ala136Val Uncertain significance ★ same type
CCDC154 p.Ala148Gly Uncertain significance ★ same type
CCDC154 p.Ala14Thr Uncertain significance ★ same type
CCDC154 p.Ala177Val Uncertain significance ★ same type
CCDC154 p.Ala205Val Uncertain significance ★ same type
CCDC154 p.Ala315Val 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/ccdc154-p-lys230gln (accessed [today's date]).

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