Is DMAC2L p.Arg24Ile (c.71G>T) pathogenic?

DMAC2L p.Arg24Ile (c.71G>T) is classified Uncertain significance in DMAC2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely pathogenic (0.7871); Absent from gnomAD v4.1.

How common is DMAC2L p.Arg24Ile (c.71G>T) in the general population?

DMAC2L p.Arg24Ile (c.71G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMAC2L p.Arg24Ile (c.71G>T)?

AlphaMissense predicts likely pathogenic (score 0.7871) — an in-silico prediction, not a clinical call.

DMAC2L p.Arg24Ile

c.71G>T · VCV3272347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7871 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.7871	likely pathogenic
REVEL	0.884	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,232 bp · p 0.63 · regional, not allelic
Overall
CADD	31.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R39I vs ClinVar R24I) — verify the residue.

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: DMAC2L
Protein: p.Arg24Ile
Coding: c.71G>T
MANE Select: NM_001382507
Type: single nucleotide variant
Location: chr14:50321558 (GRCh38)
Gene constraint: LOEUF 1.315 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.27
Residue 24: the 'n-terminal domain' region

Full DMAC2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAC2L p.Arg24Thr Uncertain significance ★ ⚠ same residue
L2HGDH p.Pro24Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
L2HGDH p.Met1Val Pathogenic ★★ same type
L2HGDH c.140+3G>C Uncertain significance ★★ same type
L2HGDH p.Ala26Val Uncertain significance ★★ ⚠ same type
L2HGDH p.Ser41Asn Uncertain significance ★★ ⚠ same type
L2HGDH p.Ala20= Likely benign ★★ same type
L2HGDH p.Leu18Arg Benign/Likely benign ★★ 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/dmac2l-p-arg24ile (accessed [today's date]).

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