Is MLNR p.Arg236Pro (c.707G>C) pathogenic?

MLNR p.Arg236Pro (c.707G>C) is classified Uncertain significance in MLNR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely pathogenic (0.7463); Ultra-rare (popmax 0.0468%, sas).

How common is MLNR p.Arg236Pro (c.707G>C) in the general population?

MLNR p.Arg236Pro (c.707G>C) is ultra-rare (popmax 0.0468%, sas) (gnomAD).

What do computational predictors say about MLNR p.Arg236Pro (c.707G>C)?

AlphaMissense predicts likely pathogenic (score 0.7463) — an in-silico prediction, not a clinical call.

MLNR p.Arg236Pro

c.707G>C · VCV3873601

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7463 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7463	likely pathogenic
REVEL	0.547	indeterminate
SaProt	LLR -12.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,036 bp · p 0.12 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0468% South Asian · 41/87,524 alleles

Filtering AF 0.0354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00281% 44/1,567,134 alleles · ultra-rare exomes 38/1,414,900 · genomes 6/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0468%	2,135
Remaining individualsnot grpmax-eligible	0.00164%	60,926
European (non-Finnish)	0.000171%	583,659

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: MLNR
Protein: p.Arg236Pro
Coding: c.707G>C
MANE Select: NM_001507
Type: single nucleotide variant
Location: chr13:49221044 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.99 · 4 PDB
Residue 236: an α-helix

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

Similar variants

MLNR p.Arg236Trp Uncertain significance ★ ⚠ same residue
MLNR p.Ala164Thr Uncertain significance ★ ⚠ same type
MLNR p.Ala198Pro Uncertain significance ★ ⚠ same type
MLNR p.Ala229Val Uncertain significance ★ ⚠ same type
MLNR p.Ala364Pro Uncertain significance ★ ⚠ same type
MLNR p.Ala406Thr Uncertain significance ★ ⚠ same type
MLNR p.Arg102Trp Uncertain significance ★ ⚠ same type
MLNR p.Arg112Gly 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/mlnr-p-arg236pro (accessed [today's date]).

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