Is ITGAL p.Pro113Ser (c.337C>T) pathogenic?

ITGAL p.Pro113Ser (c.337C>T) is classified Uncertain significance in ITGAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: ambiguous (0.3622); Very rare (popmax 0.0078%, nfe).

How common is ITGAL p.Pro113Ser (c.337C>T) in the general population?

ITGAL p.Pro113Ser (c.337C>T) is very rare (popmax 0.0078%, nfe) (gnomAD).

What do computational predictors say about ITGAL p.Pro113Ser (c.337C>T)?

AlphaMissense predicts ambiguous (score 0.3622) — an in-silico prediction, not a clinical call.

ITGAL p.Pro113Ser

c.337C>T · VCV4088399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0078%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3622	ambiguous
REVEL	0.713	pathogenic-leaning
SaProt	LLR -8.79	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.84, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,541 bp · p 0.72 · regional, not allelic
Overall
CADD	21.4	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 0.0078% European (non-Finnish) · 92/1,179,936 alleles

Filtering AF 0.00648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.00576% 93/1,613,600 alleles · very rare exomes 91/1,461,570 · genomes 2/152,030 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0078%	12,825
African / African-American	0.00134%	74,856

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: ITGAL
Protein: p.Pro113Ser
Coding: c.337C>T
MANE Select: NM_002209
Type: single nucleotide variant
Location: chr16:30479100 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.77 · 41 PDB
Residue 113: a β-strand

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

Similar variants

ITGAL c.1213+9T>G Benign ★★ same type
ITGAL p.Ala307= Benign ★★ same type
ITGAL p.Arg1020His Benign/Likely benign ★★ ⚠ same type
ITGAL p.Pro1152= Benign ★★ same type
ITGAL p.Ser891= Benign ★★ same type
ITGAL p.Ala1045Pro Uncertain significance ★ ⚠ same type
ITGAL p.Ala1072Thr Uncertain significance ★ ⚠ same type
ITGAL p.Ala1127Pro 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/itgal-p-pro113ser (accessed [today's date]).

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