Is TSPAN7 p.Ala79= (c.237T>C) pathogenic?

TSPAN7 p.Ala79= (c.237T>C) is classified Benign/Likely benign in TSPAN7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-11-28). Common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, X-linked 58.

What condition is associated with TSPAN7 p.Ala79= (c.237T>C)?

TSPAN7 p.Ala79= (c.237T>C) is associated with intellectual disability, X-linked 58 (ClinVar).

TSPAN7 p.Ala79=

Q: How common is TSPAN7 p.Ala79= (c.237T>C) in the general population?

TSPAN7 p.Ala79= (c.237T>C) is common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.237T>C · rs7049247 · VCV130644

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, X-linked 58

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 -1.3	GERP -5.4
Overall
CADD	5.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.4% African / African-American · 8,227/57,160 alleles

Filtering AF 14.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14%

Overall 0.775% 9,375/1,210,206 alleles · common exomes 4,720/1,098,185 · genomes 4,655/112,021 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.4%	7
Remaining individualsnot grpmax-eligible	1.04%	96
Admixed American	0.95%	105
Middle Eastern	0.482%	207
South Asian	0.044%	2,273
European (non-Finnish)	0.0191%	5,236
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,040

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: TSPAN7
Protein: p.Ala79=
Coding: c.237T>C
MANE Select: NM_004615
dbSNP: rs7049247
Type: single nucleotide variant
Location: chrX:38666276 (GRCh38)
Structure: AlphaFold pLDDT 89.18 · 2 PDB

Full TSPAN7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 58 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TSPAN7 p.Met209Thr Uncertain significance ★★ ⚠ same condition
TSPAN7 c.271-1G>T Likely pathogenic ★ same condition
TSPAN7 p.Tyr164Ter Pathogenic ★ same condition
TSPAN7 c.82-1G>T Uncertain significance ★ same condition
TSPAN7 p.Gly83Ala Uncertain significance ★ ⚠ same condition
TSPAN7 p.Pro172His Conflicting classifications of pathogenicity ★ ⚠ same condition
TSPAN7 p.Gly218Ter Pathogenic same condition
TSPAN7 c.-15_-13delCCG Benign ★★ 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/tspan7-p-ala79 (accessed [today's date]).

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