Is ITGA2 p.Phe198Ser (c.593T>C) pathogenic?

ITGA2 p.Phe198Ser (c.593T>C) is classified Uncertain significance in ITGA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.9762); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ITGA2 p.Phe198Ser (c.593T>C)?

ITGA2 p.Phe198Ser (c.593T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA2 p.Phe198Ser (c.593T>C) in the general population?

ITGA2 p.Phe198Ser (c.593T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITGA2 p.Phe198Ser (c.593T>C)?

AlphaMissense predicts likely pathogenic (score 0.9762) — an in-silico prediction, not a clinical call.

ITGA2 p.Phe198Ser

c.593T>C · VCV3530339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9762 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9762	likely pathogenic · top 4% in ITGA2
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -14.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 81 kb · p 0.11 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ITGA2
Protein: p.Phe198Ser
Coding: c.593T>C
MANE Select: NM_002203
Type: single nucleotide variant
Location: chr5:53048733 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 23 PDB
Residue 198: an α-helix; the vwfa domain

Full ITGA2 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

ITGA2 p.Asn57Lys Uncertain significance ★★ ⚠ same condition
ITGA2 p.Gly201Asp Uncertain significance ★★ ⚠ same condition
ITGA2 p.Gly205Val Uncertain significance ★★ ⚠ same condition
ITGA2 p.Ala1053Thr Uncertain significance ★ ⚠ same condition
ITGA2 p.Ala1085Pro Uncertain significance ★ ⚠ same condition
ITGA2 p.Ala1085Thr Uncertain significance ★ ⚠ same condition
ITGA2 p.Ala1151Gly Uncertain significance ★ ⚠ same condition
ITGA2 p.Ala274Thr 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/itga2-p-phe198ser (accessed [today's date]).

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