Is CCDC124 p.Ala26Pro (c.76G>C) pathogenic?

CCDC124 p.Ala26Pro (c.76G>C) is classified Uncertain significance in CCDC124 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.9778); Absent from gnomAD v4.1.

How common is CCDC124 p.Ala26Pro (c.76G>C) in the general population?

CCDC124 p.Ala26Pro (c.76G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC124 p.Ala26Pro (c.76G>C)?

AlphaMissense predicts likely pathogenic (score 0.9778) — an in-silico prediction, not a clinical call.

CCDC124 p.Ala26Pro

c.76G>C · VCV4648982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9778 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9778	likely pathogenic · top 9% in CCDC124
REVEL	0.18	moderately benign-leaning
SaProt	LLR -15.03	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 7,291 bp · p 0.057 · regional, not allelic
Overall
CADD	24.3	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: CCDC124
Protein: p.Ala26Pro
Coding: c.76G>C
MANE Select: NM_001136203
Type: single nucleotide variant
Location: chr19:17936496 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 80.59 · 6 PDB
Residue 26: the 'disordered' region; an α-helix

Full CCDC124 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC124 p.Ala26Thr Uncertain significance ★ ⚠ same residue
CCDC124 p.Ala160Val Uncertain significance ★ ⚠ same type
CCDC124 p.Ala161Val Uncertain significance ★ ⚠ same type
CCDC124 p.Ala86Thr Uncertain significance ★ ⚠ same type
CCDC124 p.Ala98Val Uncertain significance ★ ⚠ same type
CCDC124 p.Arg106Gln Uncertain significance ★ ⚠ same type
CCDC124 p.Arg145His Uncertain significance ★ ⚠ same type
CCDC124 p.Arg163Pro 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/ccdc124-p-ala26pro (accessed [today's date]).

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