Is MLIP p.Ala764Pro (c.2290G>C) pathogenic?

MLIP p.Ala764Pro (c.2290G>C) is classified Uncertain significance in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.9036); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with MLIP p.Ala764Pro (c.2290G>C)?

MLIP p.Ala764Pro (c.2290G>C) is associated with Inborn genetic diseases (ClinVar).

How common is MLIP p.Ala764Pro (c.2290G>C) in the general population?

MLIP p.Ala764Pro (c.2290G>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about MLIP p.Ala764Pro (c.2290G>C)?

AlphaMissense predicts likely pathogenic (score 0.9036) — an in-silico prediction, not a clinical call.

MLIP p.Ala764Pro

c.2290G>C · VCV3396794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9036	likely pathogenic · top 4% in MLIP
REVEL	0.35	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.35	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 154 kb · p 0.0046 · regional, not allelic
Overall
CADD	29.3	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 A229P vs ClinVar A764P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,850 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,611,268 alleles · very rare exomes 19/1,459,284 · genomes 6/151,984 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
European (non-Finnish)	0.00178%	56,113

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.Ala764Pro
Coding: c.2290G>C
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54160367 (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.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
MLIP p.Glu984Lys 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-ala764pro (accessed [today's date]).

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