Is CD109 p.Pro570Leu (c.1709C>T) pathogenic?

CD109 p.Pro570Leu (c.1709C>T) is classified Likely benign in CD109 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-01). AlphaMissense: ambiguous (0.4074); Rare (popmax 0.447%, nfe); Associated with multiple sclerosis.

What condition is associated with CD109 p.Pro570Leu (c.1709C>T)?

CD109 p.Pro570Leu (c.1709C>T) is associated with multiple sclerosis (ClinVar).

How common is CD109 p.Pro570Leu (c.1709C>T) in the general population?

CD109 p.Pro570Leu (c.1709C>T) is rare (popmax 0.447%, nfe) (gnomAD).

What do computational predictors say about CD109 p.Pro570Leu (c.1709C>T)?

AlphaMissense predicts ambiguous (score 0.4074) — an in-silico prediction, not a clinical call.

CD109 p.Pro570Leu

c.1709C>T · VCV3257589

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4074 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.447%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

multiple sclerosis

Computational evidence

Protein change
AlphaMissense	0.4074	ambiguous
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -14.15	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 127 kb · p 0.4 · regional, not allelic
Overall
CADD	24.0	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 0.447% European (non-Finnish) · 5,267/1,177,202 alleles

Filtering AF 0.437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.433%

Overall 0.371% 5,957/1,606,202 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.447%	224
Remaining individualsnot grpmax-eligible	0.381%	263
South Asian	0.269%	372
Middle Eastern	0.116%	864
Finnishnot grpmax-eligible	0.111%	899
Admixed American	0.111%	900
Ashkenazi Jewishnot grpmax-eligible	0.0848%	1,179
African / African-American	0.0603%	1,658
East Asian	0.00224%	44,576

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.Pro570Leu
Coding: c.1709C>T
MANE Select: NM_133493
Type: single nucleotide variant
Location: chr6:73771463 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 3 PDB

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

Disease context

multiple sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro570leu (accessed [today's date]).

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