Is MDN1 p.Ser243Phe (c.728C>T) pathogenic?

MDN1 p.Ser243Phe (c.728C>T) is classified Likely benign in MDN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-08). AlphaMissense: likely benign (0.1154); Rare (popmax 0.622%, afr); Associated with MDN1-related disorder.

What condition is associated with MDN1 p.Ser243Phe (c.728C>T)?

MDN1 p.Ser243Phe (c.728C>T) is associated with MDN1-related disorder (ClinVar).

How common is MDN1 p.Ser243Phe (c.728C>T) in the general population?

MDN1 p.Ser243Phe (c.728C>T) is rare (popmax 0.622%, afr) (gnomAD).

What do computational predictors say about MDN1 p.Ser243Phe (c.728C>T)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

MDN1 p.Ser243Phe

c.728C>T · rs77990038 · VCV3042186

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.622%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

MDN1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.49, phastCons 0.88
Regional constraint	o/e 0.95	unconstrained · MANE · 68 kb · p 0.064 · regional, not allelic
Overall
CADD	15.26	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.622% African / African-American · 467/75,032 alleles

Filtering AF 0.576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.557%

Overall 0.0317% 512/1,614,064 alleles · rare exomes 282/1,461,800 · genomes 230/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.622%	161
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.0233%	4,287
European (non-Finnish)	0.000508%	196,659

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.Ser243Phe
Coding: c.728C>T
MANE Select: NM_014611
dbSNP: rs77990038
Type: single nucleotide variant
Location: chr6:89793889 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)

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-ser243phe (accessed [today's date]).

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