Is SH2D1A p.Ser34= (c.102C>T) pathogenic?

SH2D1A p.Ser34= (c.102C>T) is classified Likely benign in SH2D1A (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-17). Very rare (popmax 0.000782%, nfe); Associated with X-linked lymphoproliferative disease due to SH2D1A deficiency.

What condition is associated with SH2D1A p.Ser34= (c.102C>T)?

SH2D1A p.Ser34= (c.102C>T) is associated with X-linked lymphoproliferative disease due to SH2D1A deficiency (ClinVar).

How common is SH2D1A p.Ser34= (c.102C>T) in the general population?

SH2D1A p.Ser34= (c.102C>T) is very rare (popmax 0.000782%, nfe) (gnomAD).

SH2D1A p.Ser34=

Q: How is X-linked lymphoproliferative disease due to SAP deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.102C>T · rs1484311033 · VCV1481815

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000782%, nfe)

Conditions

X-linked lymphoproliferative disease due to SH2D1A deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -4.2
Overall
CADD	8.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000782% European (non-Finnish) · 7/895,159 alleles

Filtering AF 0.000325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000578% 7/1,211,349 alleles · very rare exomes 7/1,097,722 · genomes 0/113,627 · joint denominator

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: SH2D1A
Protein: p.Ser34=
Coding: c.102C>T
MANE Select: NM_002351
dbSNP: rs1484311033
Type: single nucleotide variant
Location: chrX:124346744 (GRCh38)
Structure: AlphaFold pLDDT 84.53 · 6 PDB
Residue 34: the sh2 domain

Full SH2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked lymphoproliferative disease due to SH2D1A deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked lymphoproliferative disease due to SAP deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

SH2D1A p.Ser34Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
SH2D1A c.138-1G>A Pathogenic ★★ same condition
SH2D1A p.Arg55Ter Pathogenic ★★ same condition
SH2D1A p.Asp2Gly Likely pathogenic ★★ ⚠ same condition
SH2D1A p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
SH2D1A p.Trp64Ter Pathogenic ★★ same condition
SH2D1A p.Cys124Ser Uncertain significance ★★ ⚠ same condition
SH2D1A p.Ser63Pro 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/sh2d1a-p-ser34 (accessed [today's date]).

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