Is MLIP p.Thr381= (c.1143C>T) pathogenic?

MLIP p.Thr381= (c.1143C>T) is classified Likely benign in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Ultra-rare (popmax 0.0333%, mid).

How common is MLIP p.Thr381= (c.1143C>T) in the general population?

MLIP p.Thr381= (c.1143C>T) is ultra-rare (popmax 0.0333%, mid) (gnomAD).

MLIP p.Thr381=

c.1143C>T · VCV4280803

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.14	GERP -3.7
Overall
CADD	2.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Middle Eastern · 2/6,012 alleles

Filtering AF 0.00586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.000326% 5/1,535,992 alleles · ultra-rare exomes 4/1,383,850 · genomes 1/152,142 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0333%	3,006
Remaining individualsnot grpmax-eligible	0.00167%	60,000
African / African-American	0.00137%	73,026
South Asian	0.00119%	84,058

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: MLIP
Protein: p.Thr381=
Coding: c.1143C>T
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54137212 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75
Residue 381: a UniProt-annotated variant site (in mmckr1; decreased transcript level in muscle from homozygous patient, no effect on subcellular location); the 'required for interaction with isl1' region

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

Similar variants

MLIP p.Asn14Tyr Uncertain significance ★★ same type
MLIP p.Ser855Thr Benign ★★ same type
MLIP p.Thr581= Benign/Likely benign ★★ same type
MLIP c.2589+1G>A Likely pathogenic ★ same type
MLIP p.Arg844Ter Pathogenic ★ same type
MLIP p.Lys609Ter Pathogenic ★ same type
MLIP p.Ala764Pro Uncertain significance ★ same type
MLIP p.Ala941Asp 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/mlip-p-thr381 (accessed [today's date]).

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