Is DMAC2L p.Asp83Val (c.248A>T) pathogenic?

DMAC2L p.Asp83Val (c.248A>T) is classified Uncertain significance in DMAC2L (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.2107); Very rare (popmax 0.00801%, afr).

How common is DMAC2L p.Asp83Val (c.248A>T) in the general population?

DMAC2L p.Asp83Val (c.248A>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about DMAC2L p.Asp83Val (c.248A>T)?

AlphaMissense predicts likely benign (score 0.2107) — an in-silico prediction, not a clinical call.

DMAC2L p.Asp83Val

c.248A>T · rs373076938 · VCV3083002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
AlphaMissense	0.2107	likely benign
REVEL	0.398	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 2.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,232 bp · p 0.63 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D98V vs ClinVar D83V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,894 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,614,026 alleles · very 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: DMAC2L
Protein: p.Asp83Val
Coding: c.248A>T
MANE Select: NM_001382507
dbSNP: rs373076938
Type: single nucleotide variant
Location: chr14:50322651 (GRCh38)
Gene constraint: LOEUF 1.315 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.27

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

Similar variants

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
L2HGDH p.Ser23= Likely benign ★★ same type
L2HGDH p.Thr46Ile 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-asp83val (accessed [today's date]).

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