Is CCDC124 p.Ser141Ile (c.422G>T) pathogenic?

CCDC124 p.Ser141Ile (c.422G>T) is classified Uncertain significance in CCDC124 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.1731); Ultra-rare (popmax 0.0255%, afr).

How common is CCDC124 p.Ser141Ile (c.422G>T) in the general population?

CCDC124 p.Ser141Ile (c.422G>T) is ultra-rare (popmax 0.0255%, afr) (gnomAD).

What do computational predictors say about CCDC124 p.Ser141Ile (c.422G>T)?

AlphaMissense predicts likely benign (score 0.1731) — an in-silico prediction, not a clinical call.

CCDC124 p.Ser141Ile

c.422G>T · rs149667982 · VCV3138311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0255%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1731	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.47	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 1.8	phastCons 0.97
Regional constraint	o/e 0.89	unconstrained · MANE · 7,291 bp · p 0.057 · regional, not allelic
Overall
CADD	21.8	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 0.0255% African / African-American · 19/74,400 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00125% 20/1,594,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0255%	3,916
Remaining individualsnot grpmax-eligible	0.00162%	61,780

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.Ser141Ile
Coding: c.422G>T
MANE Select: NM_001136203
dbSNP: rs149667982
Type: single nucleotide variant
Location: chr19:17943333 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 80.59 · 6 PDB
Residue 141: a modified residue (phosphoserine)

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

Similar variants

CCDC124 p.Ser141Gly Uncertain significance ★ ⚠ same residue
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

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-ser141ile (accessed [today's date]).

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