Is CCDC138 p.Val348Ala (c.1043T>C) pathogenic?

CCDC138 p.Val348Ala (c.1043T>C) is classified Uncertain significance in CCDC138 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.1216); Very rare (popmax 0.00269%, afr).

How common is CCDC138 p.Val348Ala (c.1043T>C) in the general population?

CCDC138 p.Val348Ala (c.1043T>C) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about CCDC138 p.Val348Ala (c.1043T>C)?

AlphaMissense predicts likely benign (score 0.1216) — an in-silico prediction, not a clinical call.

CCDC138 p.Val348Ala

c.1043T>C · rs1684714353 · VCV2589775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1216 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1216	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.84	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 0.68	GERP -1.9, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 89 kb · p 0.038 · regional, not allelic
Overall
CADD	16.66	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 0.00269% African / African-American · 2/74,312 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000187% 3/1,603,798 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,156
European (non-Finnish)	8.5e-05%	1,176,603

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.Val348Ala
Coding: c.1043T>C
MANE Select: NM_144978
dbSNP: rs1684714353
Type: single nucleotide variant
Location: chr2:108815942 (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-val348ala (accessed [today's date]).

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