Is SAMD9 p.Asp1237Ala (c.3710A>C) pathogenic?

SAMD9 p.Asp1237Ala (c.3710A>C) is classified Uncertain significance in SAMD9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-25). AlphaMissense: likely benign (0.1234); Very rare (popmax 0.00102%, nfe); Associated with SAMD9-related disorder.

What condition is associated with SAMD9 p.Asp1237Ala (c.3710A>C)?

SAMD9 p.Asp1237Ala (c.3710A>C) is associated with SAMD9-related disorder (ClinVar).

How common is SAMD9 p.Asp1237Ala (c.3710A>C) in the general population?

SAMD9 p.Asp1237Ala (c.3710A>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about SAMD9 p.Asp1237Ala (c.3710A>C)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

SAMD9 p.Asp1237Ala

c.3710A>C · rs371082830 · VCV2632358

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SAMD9-related disorder

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.19	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 -0.036
Regional constraint	o/e 0.84	unconstrained · MANE · 2,122 bp · p 6.9e-06 · regional, not allelic
Overall
CADD	11.63	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 0.00102% European (non-Finnish) · 12/1,176,628 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000823% 12/1,457,816 alleles · very rare

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: SAMD9
Protein: p.Asp1237Ala
Coding: c.3710A>C
MANE Select: NM_017654
dbSNP: rs371082830
Type: single nucleotide variant
Location: chr7:93102388 (GRCh38)
Gene constraint: LOEUF 1.773 · pLI 0.03 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.79 · 10 PDB

Full SAMD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SAMD9-related disorder

Similar variants

SAMD9 p.Asp1237Tyr Uncertain significance ★ ⚠ same residue
SAMD9 p.Asp1237= Likely benign ★ same residue
SAMD9 p.Ala716Thr Uncertain significance ★★ ⚠ same condition
SAMD9 p.Arg1403Ser Uncertain significance ★★ ⚠ same condition
SAMD9 p.Arg902Gln Uncertain significance ★★ ⚠ same condition
SAMD9 p.Asn407Ser Uncertain significance ★★ ⚠ same condition
SAMD9 p.Gln30Arg Uncertain significance ★★ ⚠ same condition
SAMD9 p.Gly1484Arg 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/samd9-p-asp1237ala (accessed [today's date]).

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