Is DMAC1 p.Val52Leu (c.154G>T) pathogenic?

DMAC1 p.Val52Leu (c.154G>T) is classified Uncertain significance in DMAC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). Very rare (popmax 0.00297%, nfe).

How common is DMAC1 p.Val52Leu (c.154G>T) in the general population?

DMAC1 p.Val52Leu (c.154G>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

DMAC1 p.Val52Leu

c.154G>T · rs761827796 · VCV2598630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.026	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.7
Regional constraint	o/e 1.38	unconstrained · MANE · 1,158 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	0.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,180,028 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00217% 35/1,613,732 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: DMAC1
Protein: p.Val52Leu
Coding: c.154G>T
MANE Select: NM_033428
dbSNP: rs761827796
Type: single nucleotide variant
Location: chr9:7799581 (GRCh38)
Gene constraint: LOEUF 1.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.00

Full DMAC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAC1 p.Ala21Gly Uncertain significance ★ same type
DMAC1 p.Ala24Gly Uncertain significance ★ same type
DMAC1 p.Ala30Ser Uncertain significance ★ same type
DMAC1 p.Ala39Gly Uncertain significance ★ same type
DMAC1 p.Arg110Cys Uncertain significance ★ same type
DMAC1 p.Arg110His Uncertain significance ★ same type
DMAC1 p.Arg42His Uncertain significance ★ same type
DMAC1 p.Gln86Arg 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/dmac1-p-val52leu (accessed [today's date]).

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