Is MLIP p.Pro700Arg (c.2099C>G) pathogenic?

MLIP p.Pro700Arg (c.2099C>G) is classified Likely benign in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). Rare (popmax 0.278%, amr).

How common is MLIP p.Pro700Arg (c.2099C>G) in the general population?

MLIP p.Pro700Arg (c.2099C>G) is rare (popmax 0.278%, amr) (gnomAD).

MLIP p.Pro700Arg

c.2099C>G · VCV3777840

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.278%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.087	GERP -2.2
Regional constraint	o/e 1.08	unconstrained · MANE · 154 kb · p 0.0046 · regional, not allelic
Overall
CADD	3.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.278% Admixed American · 142/50,996 alleles

Filtering AF 0.241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.138% 2,122/1,536,118 alleles · rare exomes 1,951/1,383,814 · genomes 171/152,304 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.576%	174
Admixed Americangrpmax	0.278%	359
South Asian	0.152%	657
Remaining individualsnot grpmax-eligible	0.147%	682
European (non-Finnish)	0.138%	726
Middle Eastern	0.0668%	1,497
African / African-American	0.0191%	5,226
East Asian	0.00244%	40,914
Finnishnot grpmax-eligible	0.00225%	44,526

Ashkenazi Jewish 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.Pro700Arg
Coding: c.2099C>G
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54138168 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75
Residue 700: the 'disordered' region; a UniProt-annotated variant site (in mmckr1; decreased transcript level in muscle from homozygous patient, no effect on subcellular location); a UniProt-annotated variant site (in mmckr1); 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-pro700arg (accessed [today's date]).

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