Is CD109 p.Ile897Asn (c.2690T>A) pathogenic?

CD109 p.Ile897Asn (c.2690T>A) is classified Uncertain significance in CD109 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely pathogenic (0.7455); Very rare (popmax 0.00534%, afr).

How common is CD109 p.Ile897Asn (c.2690T>A) in the general population?

CD109 p.Ile897Asn (c.2690T>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CD109 p.Ile897Asn (c.2690T>A)?

AlphaMissense predicts likely pathogenic (score 0.7455) — an in-silico prediction, not a clinical call.

CD109 p.Ile897Asn

c.2690T>A · rs1313240950 · VCV2401838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7455	likely pathogenic · top 8% in CD109
REVEL	0.27	benign-leaning
SaProt	LLR -16.15	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 127 kb · p 0.4 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,864 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,612,560 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,716
East Asian	0.00223%	44,826
European (non-Finnish)	8.48e-05%	1,179,518

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.Ile897Asn
Coding: c.2690T>A
MANE Select: NM_133493
dbSNP: rs1313240950
Type: single nucleotide variant
Location: chr6:73788601 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 3 PDB
Residue 897: 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-ile897asn (accessed [today's date]).

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