Is CCDC138 p.Arg4Met (c.11G>T) pathogenic?

CCDC138 p.Arg4Met (c.11G>T) is classified Uncertain significance in CCDC138 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). AlphaMissense: ambiguous (0.3551); Ultra-rare (popmax 0.0286%, sas).

How common is CCDC138 p.Arg4Met (c.11G>T) in the general population?

CCDC138 p.Arg4Met (c.11G>T) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

What do computational predictors say about CCDC138 p.Arg4Met (c.11G>T)?

AlphaMissense predicts ambiguous (score 0.3551) — an in-silico prediction, not a clinical call.

CCDC138 p.Arg4Met

c.11G>T · rs774873611 · VCV2377060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3551 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Computational evidence

Protein change
AlphaMissense	0.3551	ambiguous
REVEL	0.369	indeterminate
SaProt	LLR -7.89	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -1.2, phastCons 0.062
Regional constraint	o/e 1.08	unconstrained · MANE · 89 kb · p 0.038 · regional, not allelic
Overall
CADD	17.59	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 0.0286% South Asian · 25/87,302 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0169%

Overall 0.00157% 25/1,591,342 alleles · ultra-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: CCDC138
Protein: p.Arg4Met
Coding: c.11G>T
MANE Select: NM_144978
dbSNP: rs774873611
Type: single nucleotide variant
Location: chr2:108786833 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.25

Full CCDC138 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC138 p.Ala133Val Uncertain significance ★ ⚠ same type
CCDC138 p.Ala166Thr Uncertain significance ★ ⚠ same type
CCDC138 p.Ala340Thr Uncertain significance ★ ⚠ same type
CCDC138 p.Ala482Thr Uncertain significance ★ ⚠ same type
CCDC138 p.Ala663Thr Uncertain significance ★ ⚠ same type
CCDC138 p.Arg142Ser Uncertain significance ★ ⚠ same type
CCDC138 p.Arg170Trp Uncertain significance ★ ⚠ same type
CCDC138 p.Arg210His 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/ccdc138-p-arg4met (accessed [today's date]).

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