Is MLN p.Pro68Thr (c.202C>A) pathogenic?

MLN p.Pro68Thr (c.202C>A) is classified Uncertain significance in MLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0772); Ultra-rare (popmax 0.0165%, mid).

How common is MLN p.Pro68Thr (c.202C>A) in the general population?

MLN p.Pro68Thr (c.202C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about MLN p.Pro68Thr (c.202C>A)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

MLN p.Pro68Thr

c.202C>A · rs528168479 · VCV2469763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.43	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 0.2	GERP -3
Overall
CADD	0.311	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,064 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00106% 17/1,610,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,064
Remaining individualsnot grpmax-eligible	0.0016%	62,306
European (non-Finnish)	0.00127%	78,510

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.Pro68Thr
Coding: c.202C>A
MANE Select: NM_001304731 · reported on NM_002418
dbSNP: rs528168479
Type: single nucleotide variant
Location: chr6:33799137 (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.Leu79Pro 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-pro68thr (accessed [today's date]).

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