Is MLXIP p.Pro439Ser (c.1315C>T) pathogenic?

MLXIP p.Pro439Ser (c.1315C>T) is classified Uncertain significance in MLXIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.0823); Absent from gnomAD v4.1.

How common is MLXIP p.Pro439Ser (c.1315C>T) in the general population?

MLXIP p.Pro439Ser (c.1315C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MLXIP p.Pro439Ser (c.1315C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

MLXIP p.Pro439Ser

c.1315C>T · rs2547052074 · VCV2265958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.85, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	17.22	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MLXIP
Protein: p.Pro439Ser
Coding: c.1315C>T
MANE Select: NM_014938
dbSNP: rs2547052074
Type: single nucleotide variant
Location: chr12:122133570 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.60
Residue 439: the 'transactivation domain' region

Full MLXIP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MLXIP c.2385-2A>G Uncertain significance ★ same type
MLXIP p.Ala203Val Uncertain significance ★ ⚠ same type
MLXIP p.Ala488Thr Uncertain significance ★ ⚠ same type
MLXIP p.Arg550Thr Uncertain significance ★ ⚠ same type
MLXIP p.Asn572Asp Uncertain significance ★ ⚠ same type
MLXIP p.Asn703Ser Uncertain significance ★ ⚠ same type
MLXIP p.Asp158Asn Uncertain significance ★ ⚠ same type
MLXIP p.Asp158Tyr 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/mlxip-p-pro439ser (accessed [today's date]).

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