Is MLX p.Asp25= (c.75C>T) pathogenic?

MLX p.Asp25= (c.75C>T) is classified Benign in MLX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-02). Rare (popmax 0.322%, sas).

How common is MLX p.Asp25= (c.75C>T) in the general population?

MLX p.Asp25= (c.75C>T) is rare (popmax 0.322%, sas) (gnomAD).

MLX p.Asp25=

c.75C>T · rs190987287 · VCV756256

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.322%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.95	GERP -2.8, phastCons 0.002
Overall
CADD	10.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.322% South Asian · 293/91,084 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.0198% 320/1,614,120 alleles · rare exomes 296/1,461,844 · genomes 24/152,276 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.322%	311
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Middle Eastern	0.0165%	6,060
East Asian	0.00891%	11,220
African / African-American	0.00267%	37,514
European (non-Finnish)	0.000339%	295,002

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.Asp25=
Coding: c.75C>T
MANE Select: NM_198204
dbSNP: rs190987287
Type: single nucleotide variant
Location: chr17:42567651 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 73.71
Residue 25: the 'disordered' region

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-asp25 (accessed [today's date]).

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