Is MDN1 p.Asp409= (c.1227C>T) pathogenic?

MDN1 p.Asp409= (c.1227C>T) is classified Benign in MDN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-23). Common (popmax 16.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with MDN1-related disorder.

What condition is associated with MDN1 p.Asp409= (c.1227C>T)?

MDN1 p.Asp409= (c.1227C>T) is associated with MDN1-related disorder (ClinVar).

MDN1 p.Asp409=

Q: How common is MDN1 p.Asp409= (c.1227C>T) in the general population?

MDN1 p.Asp409= (c.1227C>T) is common (popmax 16.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1227C>T · rs1036853 · VCV3060752

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 16.9%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

MDN1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.78 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.2	GERP -3.1
Overall
CADD	0.475	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.9% South Asian · 15,118/89,694 alleles

Filtering AF 16.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.5%

Overall 13% 208,690/1,606,016 alleles · common exomes 193,493/1,453,848 · genomes 15,197/152,168 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	16.9%	6
Amishnot grpmax-eligible	15.6%	6
Middle Eastern	14.1%	7
European (non-Finnish)	13.9%	7
Finnishnot grpmax-eligible	12.9%	8
Remaining individualsnot grpmax-eligible	12.6%	8
Ashkenazi Jewishnot grpmax-eligible	11.6%	9
Admixed American	8.98%	11
East Asian	4.64%	22
African / African-American	2.31%	43

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: MDN1
Protein: p.Asp409=
Coding: c.1227C>T
MANE Select: NM_014611
dbSNP: rs1036853
Type: single nucleotide variant
Location: chr6:89789783 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)
Residue 409: the 'aaa-atpase protomer 1' region

Full MDN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MDN1-related disorder

Similar variants

MDN1 p.Ala1307Thr Uncertain significance ★★ same condition
MDN1 c.6321+2T>C Uncertain significance ★ same condition
MDN1 p.Arg1741Gly Uncertain significance same condition
MDN1 p.Arg3278Gly Uncertain significance ⚠ same condition
MDN1 p.His2450Tyr Uncertain significance ⚠ same condition
MDN1 p.Pro4030Arg Uncertain significance ⚠ same condition
MDN1 p.Trp2748Ter Uncertain significance same condition
MDN1 c.11719+9T>G Likely benign same condition

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/mdn1-p-asp409 (accessed [today's date]).

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