Is SAMD9L p.Pro87Ser (c.259C>T) pathogenic?

SAMD9L p.Pro87Ser (c.259C>T) is classified Likely benign in SAMD9L (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-20). AlphaMissense: likely benign (0.0642); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SAMD9L p.Pro87Ser (c.259C>T)?

SAMD9L p.Pro87Ser (c.259C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9L p.Pro87Ser (c.259C>T) in the general population?

SAMD9L p.Pro87Ser (c.259C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about SAMD9L p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

SAMD9L p.Pro87Ser

c.259C>T · VCV4863903

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -4.81	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 2.2	GERP -4, phastCons 0.16
Regional constraint	o/e 1.03	unconstrained · MANE · 921 bp · p 0.59 · regional, not allelic
Overall
CADD	0.098	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 0.000169% European (non-Finnish) · 2/1,179,974 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,000 alleles · very rare exomes 2/1,461,782 · genomes 0/152,218 · joint denominator

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.Pro87Ser
Coding: c.259C>T
MANE Select: NM_152703
Type: single nucleotide variant
Location: chr7:93135713 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.85
Residue 87: the 'disordered' region

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.Pro87= Likely benign ★★ same residue
SAMD9L p.Pro87Gln Uncertain significance ★ ⚠ same residue
SAMD9L p.Pro87Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro87ser (accessed [today's date]).

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