Is MTM1 p.Asp78Val (c.233A>T) pathogenic?

MTM1 p.Asp78Val (c.233A>T) is classified Uncertain significance in MTM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-16). AlphaMissense: likely benign (0.1994); Very rare (popmax 0.0022%, amr); Associated with Inborn genetic diseases.

What condition is associated with MTM1 p.Asp78Val (c.233A>T)?

MTM1 p.Asp78Val (c.233A>T) is associated with Inborn genetic diseases, X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Asp78Val (c.233A>T) in the general population?

MTM1 p.Asp78Val (c.233A>T) is very rare (popmax 0.0022%, amr) (gnomAD).

What do computational predictors say about MTM1 p.Asp78Val (c.233A>T)?

AlphaMissense predicts likely benign (score 0.1994) — an in-silico prediction, not a clinical call.

MTM1 p.Asp78Val

c.233A>T · rs782215492 · VCV663663

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1994	likely benign
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -7.84	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.3, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 65 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% Admixed American · 1/45,520 alleles

Overall 0.000347% 4/1,153,400 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00438%	22,853
Admixed Americangrpmax	0.0022%	45,520
African / African-American	0.00179%	56,022

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MTM1
Protein: p.Asp78Val
Coding: c.233A>T
MANE Select: NM_000252
dbSNP: rs782215492
Type: single nucleotide variant
Location: chrX:150614590 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 78: the gram domain

Full MTM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked myotubular myopathy

Similar variants

MTM1 p.Asp78His Uncertain significance ★ ⚠ same residue
MTM1 c.1644+1G>A Pathogenic ★★★ same condition
MTM1 p.Arg224Ter Pathogenic ★★★ same condition
MTM1 p.Arg69Cys Pathogenic ★★★ same condition
MTM1 p.Gln451= Likely pathogenic ★★★ same condition
MTM1 p.Glu404Lys Pathogenic ★★★ same condition
MTM1 p.Pro205Leu Pathogenic ★★★ same condition
MTM1 p.Trp230Arg Likely pathogenic ★★★ same condition

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/mtm1-p-asp78val (accessed [today's date]).

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