Is DMAC1 p.Pro78His (c.233C>A) pathogenic?

DMAC1 p.Pro78His (c.233C>A) is classified Uncertain significance in DMAC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). Ultra-rare (popmax 0.0527%, sas).

How common is DMAC1 p.Pro78His (c.233C>A) in the general population?

DMAC1 p.Pro78His (c.233C>A) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

DMAC1 p.Pro78His

c.233C>A · VCV4241270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.94, phastCons 0.18
Regional constraint	o/e 1.38	unconstrained · MANE · 1,158 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	19.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0527% South Asian · 48/91,010 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00298% 48/1,613,336 alleles · ultra-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.Pro78His
Coding: c.233C>A
MANE Select: NM_033428
Type: single nucleotide variant
Location: chr9:7799502 (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-pro78his (accessed [today's date]).

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