Is MLIP p.Pro49Leu (c.146C>T) pathogenic?

MLIP p.Pro49Leu (c.146C>T) is classified Uncertain significance in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.9418); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MLIP p.Pro49Leu (c.146C>T)?

MLIP p.Pro49Leu (c.146C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MLIP p.Pro49Leu (c.146C>T) in the general population?

MLIP p.Pro49Leu (c.146C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MLIP p.Pro49Leu (c.146C>T)?

AlphaMissense predicts likely pathogenic (score 0.9418) — an in-silico prediction, not a clinical call.

MLIP p.Pro49Leu

c.146C>T · VCV3396798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9418 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9418	likely pathogenic · top 2% in MLIP
REVEL	0.278	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 154 kb · p 0.0046 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P38L vs ClinVar P49L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MLIP
Protein: p.Pro49Leu
Coding: c.146C>T
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54121496 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MLIP p.Ala764Pro Uncertain significance ★ same condition
MLIP p.Ala941Asp Uncertain significance ★ ⚠ same condition
MLIP p.Ala971Thr Uncertain significance ★ ⚠ same condition
MLIP p.Arg870Cys Uncertain significance ★ same condition
MLIP p.Asp766Glu Uncertain significance ★ same condition
MLIP p.Asp901Asn Uncertain significance ★ ⚠ same condition
MLIP p.Cys972Arg Uncertain significance ★ ⚠ same condition
MLIP p.Gln936His Uncertain significance ★ ⚠ same condition

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/mlip-p-pro49leu (accessed [today's date]).

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