Is DRAM2 p.Asp45Glu (c.135C>G) pathogenic?

DRAM2 p.Asp45Glu (c.135C>G) is classified Uncertain significance in DRAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.8944); Absent from gnomAD v4.1.

How common is DRAM2 p.Asp45Glu (c.135C>G) in the general population?

DRAM2 p.Asp45Glu (c.135C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRAM2 p.Asp45Glu (c.135C>G)?

AlphaMissense predicts likely pathogenic (score 0.8944) — an in-silico prediction, not a clinical call.

DRAM2 p.Asp45Glu

c.135C>G · rs1183869089 · VCV1511553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8944	likely pathogenic
REVEL	0.354	indeterminate
SaProt	LLR -12.01	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.69 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRAM2
Protein: p.Asp45Glu
Coding: c.135C>G
MANE Select: NM_001349884
dbSNP: rs1183869089
Type: single nucleotide variant
Location: chr1:111126291 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.35

Full DRAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRAM2 p.Asp45Asn Uncertain significance ★★ ⚠ same residue
DRAM2 p.Asp45Gly Uncertain significance ★★ ⚠ same residue
DRAM2 c.340-2A>G Pathogenic/Likely pathogenic ★★ same type
DRAM2 c.518-1G>A Likely pathogenic ★★ same type
DRAM2 c.601-1G>A Likely pathogenic ★★ same type
DRAM2 p.Gln147Ter Pathogenic/Likely pathogenic ★★ same type
DRAM2 p.Trp165Ter Pathogenic ★★ same type
DRAM2 c.199+6T>G 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/dram2-p-asp45glu (accessed [today's date]).

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