Is ITGAL p.Ser35Arg (c.105C>G) pathogenic?

ITGAL p.Ser35Arg (c.105C>G) is classified Uncertain significance in ITGAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.1362); No allele count reported in gnomAD v4.1 (AN 1,609,006).

How common is ITGAL p.Ser35Arg (c.105C>G) in the general population?

ITGAL p.Ser35Arg (c.105C>G) is no allele count reported in gnomAD v4.1 (AN 1,609,006) (gnomAD).

What do computational predictors say about ITGAL p.Ser35Arg (c.105C>G)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

ITGAL p.Ser35Arg

c.105C>G · VCV4679920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,006)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.71	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 -0.004	GERP 0.71, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 6,541 bp · p 0.72 · regional, not allelic
Overall
CADD	14.19	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

No allele count reported in gnomAD v4.1 (AN 1,609,006). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ITGAL
Protein: p.Ser35Arg
Coding: c.105C>G
MANE Select: NM_002209
Type: single nucleotide variant
Location: chr16:30474239 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.77 · 41 PDB
Residue 35: 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-ser35arg (accessed [today's date]).

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