Is ITGB4 p.Pro1417Ser (c.4249C>T) pathogenic?

ITGB4 p.Pro1417Ser (c.4249C>T) is classified Uncertain significance in ITGB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). AlphaMissense: likely benign (0.0678); Very rare (popmax 0.00414%, amr); Associated with ITGB4-related disorder.

What condition is associated with ITGB4 p.Pro1417Ser (c.4249C>T)?

ITGB4 p.Pro1417Ser (c.4249C>T) is associated with ITGB4-related disorder (ClinVar).

How common is ITGB4 p.Pro1417Ser (c.4249C>T) in the general population?

ITGB4 p.Pro1417Ser (c.4249C>T) is very rare (popmax 0.00414%, amr) (gnomAD).

What do computational predictors say about ITGB4 p.Pro1417Ser (c.4249C>T)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

ITGB4 p.Pro1417Ser

c.4249C>T · rs2545861309 · VCV2634461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00414%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ITGB4-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 1e-07 · regional, not allelic
Overall
CADD	17.03	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 0.00414% Admixed American · 1/24,146 alleles

Filtering AF 3.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000232% 3/1,292,870 alleles · very rare exomes 3/1,140,846 · genomes 0/152,024 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00414%	24,146
European (non-Finnish)	0.000195%	513,255

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: ITGB4
Protein: p.Pro1417Ser
Coding: c.4249C>T
MANE Select: NM_000213
dbSNP: rs2545861309
Type: single nucleotide variant
Location: chr17:75753905 (GRCh38)

Full ITGB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITGB4-related disorder

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/itgb4-p-pro1417ser (accessed [today's date]).

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