Is CD109 p.Thr1241= (c.3723G>T) pathogenic?

CD109 p.Thr1241= (c.3723G>T) is classified Benign in CD109 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-05). Common (popmax 8.19%, afr) — too common for a highly-penetrant pathogenic allele.

CD109 p.Thr1241=

Q: How common is CD109 p.Thr1241= (c.3723G>T) in the general population?

CD109 p.Thr1241= (c.3723G>T) is common (popmax 8.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3723G>T · rs61063525 · VCV776136

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 8.19%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.49	GERP -3.7
Overall
CADD	0.924	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.19% African / African-American · 6,132/74,838 alleles

Filtering AF 8.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.95%

Overall 0.438% 7,045/1,609,406 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.19%	12
Admixed American	0.635%	157
Remaining individualsnot grpmax-eligible	0.555%	180
Middle Eastern	0.48%	208
East Asian	0.0268%	3,735
South Asian	0.0133%	7,514
European (non-Finnish)	0.0115%	8,720

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: CD109
Protein: p.Thr1241=
Coding: c.3723G>T
MANE Select: NM_133493
dbSNP: rs61063525
Type: single nucleotide variant
Location: chr6:73812225 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 3 PDB
Residue 1241: a β-strand; a UniProt-annotated variant site (in)

Full CD109 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD109 p.Gln416Glu Likely benign ★★ same type
CD109 p.Ile206Val Benign ★★ same type
CD109 p.Ala1104Val Uncertain significance ★ ⚠ same type
CD109 p.Ala1115Gly Uncertain significance ★ ⚠ same type
CD109 p.Ala1148Gly Uncertain significance ★ ⚠ same type
CD109 p.Ala1190Pro Uncertain significance ★ ⚠ same type
CD109 p.Ala1196Asp Uncertain significance ★ ⚠ same type
CD109 p.Ala1196Val 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/cd109-p-thr1241 (accessed [today's date]).

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