Is TIAM1 p.Gly1026Val (c.3077G>T) pathogenic?

TIAM1 p.Gly1026Val (c.3077G>T) is classified Uncertain significance in TIAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0837); Absent from gnomAD v4.1.

How common is TIAM1 p.Gly1026Val (c.3077G>T) in the general population?

TIAM1 p.Gly1026Val (c.3077G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TIAM1 p.Gly1026Val (c.3077G>T)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

TIAM1 p.Gly1026Val

c.3077G>T · VCV4975787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 0.62, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 40 kb · p 0.31 · regional, not allelic
Overall
CADD	18.06	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: TIAM1
Protein: p.Gly1026Val
Coding: c.3077G>T
MANE Select: NM_001353694
Type: single nucleotide variant
Location: chr21:31154341 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 59.82 · 10 PDB
Residue 1026: the 'disordered' region

Full TIAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TIAM1 p.Ala1004Thr Uncertain significance ★★ ⚠ same type
TIAM1 p.Ala549Val Uncertain significance ★★ ⚠ same type
TIAM1 p.Arg678His Uncertain significance ★★ ⚠ same type
TIAM1 p.Glu144Lys Uncertain significance ★★ ⚠ same type
TIAM1 p.Glu1567Asp Uncertain significance ★★ ⚠ same type
TIAM1 p.His1010Pro Uncertain significance ★★ ⚠ same type
TIAM1 p.Leu232Ser Uncertain significance ★★ ⚠ same type
TIAM1 p.Lys886Arg 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/tiam1-p-gly1026val (accessed [today's date]).

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