Is CD109 p.Ala836Val (c.2507C>T) pathogenic?

CD109 p.Ala836Val (c.2507C>T) is classified Uncertain significance in CD109 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1884); Rare (popmax 0.504%, afr).

How common is CD109 p.Ala836Val (c.2507C>T) in the general population?

CD109 p.Ala836Val (c.2507C>T) is rare (popmax 0.504%, afr) (gnomAD).

What do computational predictors say about CD109 p.Ala836Val (c.2507C>T)?

AlphaMissense predicts likely benign (score 0.1884) — an in-silico prediction, not a clinical call.

CD109 p.Ala836Val

c.2507C>T · VCV4222498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1884 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.504%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1884	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 127 kb · p 0.4 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.504% African / African-American · 378/75,022 alleles

Filtering AF 0.462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.445%

Overall 0.0271% 437/1,614,030 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.504%	198
Admixed American	0.0433%	2,309
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Middle Eastern	0.0165%	6,060
South Asian	0.0011%	91,072
European (non-Finnish)	0.000678%	147,492

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.Ala836Val
Coding: c.2507C>T
MANE Select: NM_133493
Type: single nucleotide variant
Location: chr6:73787403 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 3 PDB
Residue 836: a β-strand

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-ala836val (accessed [today's date]).

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