Is MLX p.Val232Ala (c.695T>C) pathogenic?

MLX p.Val232Ala (c.695T>C) is classified Uncertain significance in MLX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: ambiguous (0.4234); Very rare (popmax 0.00133%, afr).

How common is MLX p.Val232Ala (c.695T>C) in the general population?

MLX p.Val232Ala (c.695T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about MLX p.Val232Ala (c.695T>C)?

AlphaMissense predicts ambiguous (score 0.4234) — an in-silico prediction, not a clinical call.

MLX p.Val232Ala

c.695T>C · rs2093032811 · VCV3211029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4234	ambiguous
REVEL	0.706	pathogenic-leaning
SaProt	LLR -10.15	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,475 bp · p 0.22 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V286A vs ClinVar V232A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,950 alleles

Overall 0.000657% 1/152,232 alleles · very rare

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: MLX
Protein: p.Val232Ala
Coding: c.695T>C
MANE Select: NM_198204
dbSNP: rs2093032811
Type: single nucleotide variant
Location: chr17:42571563 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 73.71

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

Similar variants

MLX p.Gln169Arg Benign ★★ same type
PSMC3IP c.*9C>T Benign ★★ same type
MLX p.Arg229Gln Uncertain significance ★ ⚠ same type
MLX p.Arg229Trp Uncertain significance ★ ⚠ same type
MLX p.Arg34Cys Uncertain significance ★ ⚠ same type
MLX p.Asn200Ser Uncertain significance ★ ⚠ same type
MLX p.Gln115His Uncertain significance ★ ⚠ same type
MLX p.Gln140Arg 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/mlx-p-val232ala (accessed [today's date]).

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