Is NEXMIF p.Asp381Val (c.1142A>T) pathogenic?

NEXMIF p.Asp381Val (c.1142A>T) is classified Uncertain significance in NEXMIF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.1361); Absent from gnomAD v4.1; Associated with X-linked intellectual disability, Cantagrel type.

What condition is associated with NEXMIF p.Asp381Val (c.1142A>T)?

NEXMIF p.Asp381Val (c.1142A>T) is associated with X-linked intellectual disability, Cantagrel type (ClinVar).

How common is NEXMIF p.Asp381Val (c.1142A>T) in the general population?

NEXMIF p.Asp381Val (c.1142A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEXMIF p.Asp381Val (c.1142A>T)?

AlphaMissense predicts likely benign (score 0.1361) — an in-silico prediction, not a clinical call.

NEXMIF p.Asp381Val

c.1142A>T · rs2519915780 · VCV2434337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1361 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked intellectual disability, Cantagrel type

Computational evidence

Protein change
AlphaMissense	0.1361	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.28	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,872 bp · p 0.035 · regional, not allelic
Overall
CADD	23.8	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: NEXMIF
Protein: p.Asp381Val
Coding: c.1142A>T
MANE Select: NM_001008537
dbSNP: rs2519915780
Type: single nucleotide variant
Location: chrX:74743415 (GRCh38)
Structure: AlphaFold pLDDT 40.87
Residue 381: the 'disordered' region; a UniProt-annotated variant site (in xlid98; de novo dominant mutation found in females; disease phenotype includes epilepsy as a feature)

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

Disease context

X-linked intellectual disability, Cantagrel type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEXMIF p.Arg218Ter Pathogenic ★★ same condition
NEXMIF p.Arg313Ter Pathogenic ★★ same condition
NEXMIF p.Arg322Ter Pathogenic ★★ same condition
NEXMIF p.Arg348Ter Pathogenic ★★ same condition
NEXMIF p.Arg481Ter Pathogenic ★★ same condition
NEXMIF p.Arg628Ter Pathogenic ★★ same condition
NEXMIF p.Gln1137Ter Pathogenic ★★ same condition
NEXMIF p.Gln476Ter Pathogenic/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/nexmif-p-asp381val (accessed [today's date]).

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