Is MLIP p.Pro911Ser (c.2731C>T) pathogenic?

MLIP p.Pro911Ser (c.2731C>T) is classified Benign in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-06). AlphaMissense: likely benign (0.0758); Common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about MLIP p.Pro911Ser (c.2731C>T)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

MLIP p.Pro911Ser

Q: How common is MLIP p.Pro911Ser (c.2731C>T) in the general population?

MLIP p.Pro911Ser (c.2731C>T) is common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2731C>T · VCV4769474

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -1.9
Regional constraint	o/e 1.08	unconstrained · MANE · 154 kb · p 0.0046 · regional, not allelic
Overall
CADD	12.39	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 P376S vs ClinVar P911S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.6% African / African-American · 16,140/74,872 alleles

Filtering AF 21.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.2%

Overall 8.13% 131,140/1,613,398 alleles · common exomes 112,878/1,461,380 · genomes 18,262/152,018 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.6%	5
East Asian	20.6%	5
Middle Eastern	18.9%	5
Ashkenazi Jewishnot grpmax-eligible	16.6%	6
South Asian	14.8%	7
Admixed American	14.6%	7
Remaining individualsnot grpmax-eligible	9.93%	10
Amishnot grpmax-eligible	6.26%	16
European (non-Finnish)	5.76%	17
Finnishnot grpmax-eligible	5.14%	19

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.Pro911Ser
Coding: c.2731C>T
MANE Select: NM_001281747
Type: single nucleotide variant
Location: chr6:54230726 (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

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-pro911ser (accessed [today's date]).

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