Is DMAC1 p.Pro35Leu (c.104C>T) pathogenic?

DMAC1 p.Pro35Leu (c.104C>T) is classified Uncertain significance in DMAC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). Absent from gnomAD v4.1.

How common is DMAC1 p.Pro35Leu (c.104C>T) in the general population?

DMAC1 p.Pro35Leu (c.104C>T) is absent from gnomAD v4.1 (gnomAD).

DMAC1 p.Pro35Leu

c.104C>T · rs1818701583 · VCV2613448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.059	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.051, phastCons 0.73
Regional constraint	o/e 1.38	unconstrained · MANE · 1,158 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	19.82	PHRED · no single calibrated threshold — expert panels disagree

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: DMAC1
Protein: p.Pro35Leu
Coding: c.104C>T
MANE Select: NM_033428
dbSNP: rs1818701583
Type: single nucleotide variant
Location: chr9:7799631 (GRCh38)
Gene constraint: LOEUF 1.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.00
Residue 35: the 'disordered' region

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

Similar variants

DMAC1 p.Pro35Ser Uncertain significance ★ same residue
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

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-pro35leu (accessed [today's date]).

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