Is CCDC124 p.Arg88Trp (c.262C>T) pathogenic?

CCDC124 p.Arg88Trp (c.262C>T) is classified Uncertain significance in CCDC124 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.1764); Very rare (popmax 8.72e-05%, nfe).

How common is CCDC124 p.Arg88Trp (c.262C>T) in the general population?

CCDC124 p.Arg88Trp (c.262C>T) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC124 p.Arg88Trp (c.262C>T)?

AlphaMissense predicts likely benign (score 0.1764) — an in-silico prediction, not a clinical call.

CCDC124 p.Arg88Trp

c.262C>T · VCV3996383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1764 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1764	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	phastCons 0.98
Regional constraint	o/e 0.89	unconstrained · MANE · 7,291 bp · p 0.057 · regional, not allelic
Overall
CADD	23.9	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 8.72e-05% European (non-Finnish) · 1/1,146,618 alleles

Overall 7.16e-05% 1/1,396,182 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: CCDC124
Protein: p.Arg88Trp
Coding: c.262C>T
MANE Select: NM_001136203
Type: single nucleotide variant
Location: chr19:17942758 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 80.59 · 6 PDB
Residue 88: the 'disordered' region

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

Similar variants

CCDC124 p.Ala160Val Uncertain significance ★ ⚠ same type
CCDC124 p.Ala161Val Uncertain significance ★ ⚠ same type
CCDC124 p.Ala26Pro Uncertain significance ★ ⚠ same type
CCDC124 p.Ala26Thr 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

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-arg88trp (accessed [today's date]).

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