Is MLIP p.His339= (c.1017C>T) pathogenic?

MLIP p.His339= (c.1017C>T) is classified Likely benign in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-02). Very rare (popmax 0.00959%, nfe).

How common is MLIP p.His339= (c.1017C>T) in the general population?

MLIP p.His339= (c.1017C>T) is very rare (popmax 0.00959%, nfe) (gnomAD).

MLIP p.His339=

c.1017C>T · VCV4892416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00959%, 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 1.3	GERP 0.16, phastCons 0.27
Overall
CADD	7.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00959% European (non-Finnish) · 110/1,146,884 alleles

Filtering AF 0.00813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00757%

Overall 0.0176% 271/1,536,086 alleles · very rare exomes 213/1,383,820 · genomes 58/152,266 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.303%	330
Remaining individualsnot grpmax-eligible	0.0317%	3,159
Ashkenazi Jewishnot grpmax-eligible	0.0105%	9,551
European (non-Finnish)grpmax	0.00959%	10,426
East Asian	0.00733%	13,636
South Asian	0.00119%	84,054

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His339=
Coding: c.1017C>T
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54137086 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75
Residue 339: 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; the 'disordered' 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-his339 (accessed [today's date]).

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