Is INTU p.Asp28Val (c.83A>T) pathogenic?

INTU p.Asp28Val (c.83A>T) is classified Uncertain significance in INTU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-24). AlphaMissense: likely benign (0.084); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with INTU p.Asp28Val (c.83A>T)?

INTU p.Asp28Val (c.83A>T) is associated with Inborn genetic diseases (ClinVar).

How common is INTU p.Asp28Val (c.83A>T) in the general population?

INTU p.Asp28Val (c.83A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about INTU p.Asp28Val (c.83A>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

INTU p.Asp28Val

c.83A>T · rs1726908847 · VCV2977235

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.64	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 3.4	GERP -3.3, phastCons 0.97
Regional constraint	o/e 0.96	unconstrained · MANE · 83 kb · p 0.19 · regional, not allelic
Overall
CADD	18.97	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

Grpmax group 0.00133% African / African-American · 1/75,050 alleles

Overall 6.2e-05% 1/1,614,072 alleles · very rare exomes 1/1,461,742 · genomes 0/152,330 · joint denominator

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: INTU
Protein: p.Asp28Val
Coding: c.83A>T
MANE Select: NM_015693
dbSNP: rs1726908847
Type: single nucleotide variant
Location: chr4:127633117 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.35 · 4 PDB
Residue 28: the 'disordered' region

Full INTU 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

Similar variants

INTU p.Ala611Thr Uncertain significance ★★ ⚠ same condition
INTU p.Ala804Val Uncertain significance ★★ ⚠ same condition
INTU p.Arg119Thr Uncertain significance ★★ ⚠ same condition
INTU p.Arg127Cys Uncertain significance ★★ ⚠ same condition
INTU p.Arg510Trp Uncertain significance ★★ ⚠ same condition
INTU p.Arg665Cys Uncertain significance ★★ ⚠ same condition
INTU p.Arg705Cys Uncertain significance ★★ ⚠ same condition
INTU p.Asp135Gly Uncertain significance ★★ ⚠ 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/intu-p-asp28val (accessed [today's date]).

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