Is SAMD9L p.Val23= (c.69A>G) pathogenic?

SAMD9L p.Val23= (c.69A>G) is classified Likely benign in SAMD9L (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-20). Ultra-rare (popmax 0.0281%, afr); Associated with Inborn genetic diseases.

What condition is associated with SAMD9L p.Val23= (c.69A>G)?

SAMD9L p.Val23= (c.69A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9L p.Val23= (c.69A>G) in the general population?

SAMD9L p.Val23= (c.69A>G) is ultra-rare (popmax 0.0281%, afr) (gnomAD).

SAMD9L p.Val23=

c.69A>G · rs369917648 · VCV2139062

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -3.9, phastCons 0.99
Overall
CADD	1.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0281% African / African-American · 21/74,856 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00143% 23/1,612,562 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0281%	3,565
Admixed American	0.00335%	29,855

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: SAMD9L
Protein: p.Val23=
Coding: c.69A>G
MANE Select: NM_152703
dbSNP: rs369917648
Type: single nucleotide variant
Location: chr7:93135903 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.85
Residue 23: the sam domain

Full SAMD9L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SAMD9L p.Ala1073Thr Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1087Asp Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1106Thr Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1106Val Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1109Pro Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1156Glu Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1156Ser Uncertain significance ★★ ⚠ same condition
SAMD9L p.Ala1159Pro Uncertain significance ★★ ⚠ same condition

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/samd9l-p-val23 (accessed [today's date]).

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