Is MDN1 p.Arg697Cys (c.2089C>T) pathogenic?

MDN1 p.Arg697Cys (c.2089C>T) is classified Uncertain significance in MDN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.027%, nfe).

How common is MDN1 p.Arg697Cys (c.2089C>T) in the general population?

MDN1 p.Arg697Cys (c.2089C>T) is ultra-rare (popmax 0.027%, nfe) (gnomAD).

What do computational predictors say about MDN1 p.Arg697Cys (c.2089C>T)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

MDN1 p.Arg697Cys

c.2089C>T · rs200838047 · VCV2402024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.26	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	Δ0.33	acceptor loss · deltas
Pangolin	Δ0.25	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.2	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 68 kb · p 0.064 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.027% European (non-Finnish) · 318/1,179,664 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.0206% 332/1,613,568 alleles · ultra-rare exomes 323/1,461,324 · genomes 9/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.027%	3,710
Remaining individualsnot grpmax-eligible	0.0112%	8,926
South Asian	0.0044%	22,753
African / African-American	0.004%	25,003

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.Arg697Cys
Coding: c.2089C>T
MANE Select: NM_014611
dbSNP: rs200838047
Type: single nucleotide variant
Location: chr6:89771616 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)
Residue 697: the 'aaa-atpase protomer 2' region

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

Similar variants

MDN1 p.Arg697His Uncertain significance ★ ⚠ same residue
MDN1 p.Ala1307Thr Uncertain significance ★★ same type
MDN1 c.6321+2T>C Uncertain significance ★ same type
MDN1 p.Ala1098Gly Uncertain significance ★ same type
MDN1 p.Ala152Thr Uncertain significance ★ ⚠ same type
MDN1 p.Ala1791Thr Uncertain significance ★ ⚠ same type
MDN1 p.Ala1812Gly Uncertain significance ★ ⚠ same type
MDN1 p.Ala18Gly 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/mdn1-p-arg697cys (accessed [today's date]).

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