Is MLIP p.Thr581= (c.1743G>A) pathogenic?

MLIP p.Thr581= (c.1743G>A) is classified Benign/Likely benign in MLIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Rare (popmax 0.644%, nfe).

How common is MLIP p.Thr581= (c.1743G>A) in the general population?

MLIP p.Thr581= (c.1743G>A) is rare (popmax 0.644%, nfe) (gnomAD).

MLIP p.Thr581=

c.1743G>A · VCV3257587

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.644%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.5	GERP -4.2
Overall
CADD	0.284	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.644% European (non-Finnish) · 7,384/1,146,872 alleles

Filtering AF 0.632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.626%

Overall 0.517% 7,938/1,535,966 alleles · rare exomes 7,409/1,383,792 · genomes 529/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.644%	155
Remaining individualsnot grpmax-eligible	0.43%	233
Ashkenazi Jewishnot grpmax-eligible	0.352%	284
Admixed American	0.167%	600
African / African-American	0.107%	937
Finnishnot grpmax-eligible	0.0652%	1,534
Middle Eastern	0.0167%	5,990
South Asian	0.00238%	42,019

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.Thr581=
Coding: c.1743G>A
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54137812 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75
Residue 581: the 'disordered' region; 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 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
MLIP p.Ala971Thr 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-thr581 (accessed [today's date]).

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