Is CD109 p.Leu641Phe (c.1923G>T) pathogenic?

CD109 p.Leu641Phe (c.1923G>T) is classified Benign in CD109 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-14). AlphaMissense: likely benign (0.1141); Common (popmax 9.16%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CD109 p.Leu641Phe (c.1923G>T)?

AlphaMissense predicts likely benign (score 0.1141) — an in-silico prediction, not a clinical call.

CD109 p.Leu641Phe

Q: How common is CD109 p.Leu641Phe (c.1923G>T) in the general population?

CD109 p.Leu641Phe (c.1923G>T) is common (popmax 9.16%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1923G>T · rs7742662 · VCV776133

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1141 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.16%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1141	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.99	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 -0.95, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 127 kb · p 0.4 · regional, not allelic
Overall
CADD	16.0	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 9.16% African / African-American · 6,862/74,912 alleles

Filtering AF 8.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.9%

Overall 0.539% 8,687/1,613,036 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.16%	11
Remaining individualsnot grpmax-eligible	0.768%	130
Admixed American	0.765%	131
East Asian	0.602%	166
Middle Eastern	0.545%	183
Ashkenazi Jewishnot grpmax-eligible	0.21%	477
European (non-Finnish)	0.0416%	2,407
South Asian	0.0341%	2,936

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.Leu641Phe
Coding: c.1923G>T
MANE Select: NM_133493
dbSNP: rs7742662
Type: single nucleotide variant
Location: chr6:73781279 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.42 · 3 PDB
Residue 641: a UniProt-annotated variant site (in); the 'bait region (approximate)' region; 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-leu641phe (accessed [today's date]).

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