Is MAL2 p.Phe77Ser (c.230T>C) pathogenic?

MAL2 p.Phe77Ser (c.230T>C) is classified Uncertain significance in MAL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.1822); Absent from gnomAD v4.1.

How common is MAL2 p.Phe77Ser (c.230T>C) in the general population?

MAL2 p.Phe77Ser (c.230T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAL2 p.Phe77Ser (c.230T>C)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

MAL2 p.Phe77Ser

c.230T>C · VCV4102516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.74, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.52 · regional, not allelic
Overall
CADD	21.5	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; SaProt is an independent agreement signal.

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: MAL2
Protein: p.Phe77Ser
Coding: c.230T>C
MANE Select: NM_052886
Type: single nucleotide variant
Location: chr8:119221684 (GRCh38)
Gene constraint: LOEUF 1.6 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.42
Residue 77: the marvel domain

Full MAL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAL2 p.Ala15Thr Uncertain significance ★ ⚠ same type
MAL2 p.Asn13Lys Uncertain significance ★ same type
MAL2 p.Asn147Ser Uncertain significance ★ ⚠ same type
MAL2 p.Gly4Asp Uncertain significance ★ ⚠ same type
MAL2 p.Gly4Ser Uncertain significance ★ ⚠ same type
MAL2 p.Gly4Val Uncertain significance ★ ⚠ same type
MAL2 p.Gly84Ala Uncertain significance ★ ⚠ same type
MAL2 p.Leu119Ser 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/mal2-p-phe77ser (accessed [today's date]).

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