Is MLN p.Leu79Pro (c.236T>C) pathogenic?

MLN p.Leu79Pro (c.236T>C) is classified Uncertain significance in MLN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.2944); Very rare (popmax 0.000522%, nfe).

How common is MLN p.Leu79Pro (c.236T>C) in the general population?

MLN p.Leu79Pro (c.236T>C) is very rare (popmax 0.000522%, nfe) (gnomAD).

What do computational predictors say about MLN p.Leu79Pro (c.236T>C)?

AlphaMissense predicts likely benign (score 0.2944) — an in-silico prediction, not a clinical call.

MLN p.Leu79Pro

c.236T>C · VCV3396855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000522%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2944	likely benign
REVEL	0.662	pathogenic-leaning
SaProt	LLR -5.10	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.95 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.1	GERP 1.9, phastCons 1
Overall
CADD	27.7	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 0.000522% European (non-Finnish) · 6/1,148,336 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000428% 6/1,402,774 alleles · very rare

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: MLN
Protein: p.Leu79Pro
Coding: c.236T>C
MANE Select: NM_001304731 · reported on NM_002418
Type: single nucleotide variant
Location: chr6:33795604 (GRCh38)
Structure: AlphaFold pLDDT 81.26

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

Similar variants

MLN p.Ala9Val Uncertain significance ★ ⚠ same type
MLN p.Arg43Trp Uncertain significance ★ ⚠ same type
MLN p.Gln47Arg Uncertain significance ★ ⚠ same type
MLN p.Glu75Gly Uncertain significance ★ ⚠ same type
MLN p.Gly103Arg Uncertain significance ★ ⚠ same type
MLN p.Ile69Asn Uncertain significance ★ ⚠ same type
MLN p.Leu11Gln Uncertain significance ★ same type
MLN p.Leu94Val 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/mln-p-leu79pro (accessed [today's date]).

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