Is ITGB4 p.Pro341Arg (c.1022C>G) pathogenic?

ITGB4 p.Pro341Arg (c.1022C>G) is classified Uncertain significance in ITGB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: ambiguous (0.5424); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ITGB4 p.Pro341Arg (c.1022C>G)?

ITGB4 p.Pro341Arg (c.1022C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ITGB4 p.Pro341Arg (c.1022C>G) in the general population?

ITGB4 p.Pro341Arg (c.1022C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ITGB4 p.Pro341Arg (c.1022C>G)?

AlphaMissense predicts ambiguous (score 0.5424) — an in-silico prediction, not a clinical call.

ITGB4 p.Pro341Arg

c.1022C>G · VCV3861706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5424	ambiguous
REVEL	0.82	moderately pathogenic-leaning
SaProt	LLR -7.20	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 1e-07 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,030 alleles

Overall 0.000124% 2/1,613,640 alleles · very rare exomes 2/1,461,350 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,030
European (non-Finnish)	8.48e-05%	1,179,924

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.Pro341Arg
Coding: c.1022C>G
MANE Select: NM_000213
Type: single nucleotide variant
Location: chr17:75730894 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.04 · 13 PDB

Full ITGB4 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

ITGB4 p.Ala1033Val Uncertain significance ★★ same condition
ITGB4 p.Ala315Thr Uncertain significance ★★ ⚠ same condition
ITGB4 p.Ala691Thr Uncertain significance ★★ ⚠ same condition
ITGB4 p.Arg1003His Uncertain significance ★★ ⚠ same condition
ITGB4 p.Arg1077His Uncertain significance ★★ ⚠ same condition
ITGB4 p.Arg107Gln Uncertain significance ★★ ⚠ same condition
ITGB4 p.Arg107Trp Uncertain significance ★★ ⚠ same condition
ITGB4 p.Arg1301Cys 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/itgb4-p-pro341arg (accessed [today's date]).

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