Is CD109 p.Ile350Val (c.1048A>G) pathogenic?

CD109 p.Ile350Val (c.1048A>G) is classified Uncertain significance in CD109 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.0829); Ultra-rare (popmax 0.0166%, mid).

How common is CD109 p.Ile350Val (c.1048A>G) in the general population?

CD109 p.Ile350Val (c.1048A>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CD109 p.Ile350Val (c.1048A>G)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

CD109 p.Ile350Val

c.1048A>G · rs912040605 · VCV3140271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -2.3, phastCons 0.95
Regional constraint	o/e 1.02	unconstrained · MANE · 127 kb · p 0.4 · regional, not allelic
Overall
CADD	10.04	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 0.0166% Middle Eastern · 1/6,018 alleles

Filtering AF 0.000362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.000692% 10/1,444,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,018
European (non-Finnish)	0.000769%	130,083

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.Ile350Val
Coding: c.1048A>G
MANE Select: NM_133493
dbSNP: rs912040605
Type: single nucleotide variant
Location: chr6:73763626 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 3 PDB
Residue 350: 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-ile350val (accessed [today's date]).

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