Is MLNR p.Pro103Ser (c.307C>T) pathogenic?

MLNR p.Pro103Ser (c.307C>T) is classified Uncertain significance in MLNR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.847); Very rare (popmax 0.00136%, nfe).

How common is MLNR p.Pro103Ser (c.307C>T) in the general population?

MLNR p.Pro103Ser (c.307C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about MLNR p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely pathogenic (score 0.847) — an in-silico prediction, not a clinical call.

MLNR p.Pro103Ser

c.307C>T · rs139964744 · VCV2614362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.847	likely pathogenic
REVEL	0.481	indeterminate
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,036 bp · p 0.12 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,178,858 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00106% 17/1,610,276 alleles · very rare exomes 13/1,458,282 · genomes 4/151,994 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,316
European (non-Finnish)grpmax	0.00136%	73,678

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro103Ser
Coding: c.307C>T
MANE Select: NM_001507
dbSNP: rs139964744
Type: single nucleotide variant
Location: chr13:49220644 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.99 · 4 PDB

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

Similar variants

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
MLNR p.Arg112His 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-pro103ser (accessed [today's date]).

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