Is CCDC137 p.Ala2Ser (c.4G>T) pathogenic?

CCDC137 p.Ala2Ser (c.4G>T) is classified Uncertain significance in CCDC137 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.1627); Absent from gnomAD v4.1.

How common is CCDC137 p.Ala2Ser (c.4G>T) in the general population?

CCDC137 p.Ala2Ser (c.4G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC137 p.Ala2Ser (c.4G>T)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

CCDC137 p.Ala2Ser

c.4G>T · VCV3996443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,468,942)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.53	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 4.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 5,934 bp · p 0.06 · regional, not allelic
Overall
CADD	20.3	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

No allele count reported in gnomAD v4.1 (AN 1,468,942). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCDC137
Protein: p.Ala2Ser
Coding: c.4G>T
MANE Select: NM_199287
Type: single nucleotide variant
Location: chr17:81666770 (GRCh38)
Gene constraint: LOEUF 1.308 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.94
Residue 2: the 'disordered' region

Full CCDC137 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC137 p.Ala2Val Uncertain significance ★ ⚠ same residue
CCDC137 p.Ala2= Likely benign ★ same residue
CCDC137 p.Arg247Cys Uncertain significance ★★ ⚠ same type
CCDC137 p.Ala144Thr Uncertain significance ★ ⚠ same type
CCDC137 p.Ala261Val Uncertain significance ★ ⚠ same type
CCDC137 p.Ala9Glu Uncertain significance ★ ⚠ same type
CCDC137 p.Ala9Val Uncertain significance ★ ⚠ same type
CCDC137 p.Arg12Ser 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/ccdc137-p-ala2ser (accessed [today's date]).

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