Is MLNR p.Ser276Arg (c.828C>G) pathogenic?

MLNR p.Ser276Arg (c.828C>G) is classified Likely benign in MLNR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely benign (0.0751); Very rare (popmax 6.3e-05%).

How common is MLNR p.Ser276Arg (c.828C>G) in the general population?

MLNR p.Ser276Arg (c.828C>G) is very rare (popmax 6.3e-05%) (gnomAD).

What do computational predictors say about MLNR p.Ser276Arg (c.828C>G)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

MLNR p.Ser276Arg

c.828C>G · rs748956186 · VCV2603653

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.3e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -3.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.8, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 2,036 bp · p 0.12 · regional, not allelic
Overall
CADD	12.76	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 6.3e-05%

Overall 6.3e-05% 1/1,587,974 alleles · very rare exomes 1/1,435,722 · genomes 0/152,252 · joint denominator

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.Ser276Arg
Coding: c.828C>G
MANE Select: NM_001507
dbSNP: rs748956186
Type: single nucleotide variant
Location: chr13:49221165 (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-ser276arg (accessed [today's date]).

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