Is SAMD9 p.Val830Met (c.2488G>A) pathogenic?

SAMD9 p.Val830Met (c.2488G>A) is classified Uncertain significance in SAMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.6652); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with SAMD9 p.Val830Met (c.2488G>A)?

SAMD9 p.Val830Met (c.2488G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9 p.Val830Met (c.2488G>A) in the general population?

SAMD9 p.Val830Met (c.2488G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about SAMD9 p.Val830Met (c.2488G>A)?

AlphaMissense predicts likely pathogenic (score 0.6652) — an in-silico prediction, not a clinical call.

SAMD9 p.Val830Met

c.2488G>A · VCV3949555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6652	likely pathogenic
REVEL	0.469	indeterminate
SaProt	LLR -10.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 148 bp · p 0.64 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,018 alleles

Overall 6.2e-05% 1/1,613,434 alleles · very rare exomes 1/1,461,310 · genomes 0/152,124 · 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: SAMD9
Protein: p.Val830Met
Coding: c.2488G>A
MANE Select: NM_017654
Type: single nucleotide variant
Location: chr7:93103610 (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

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

Similar variants

SAMD9 p.Val830Ala Uncertain significance ★ same residue
SAMD9 p.Ala1057Val Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1066Thr Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1069Thr Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1082Gly Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1102Asp Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1195Asp Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala123Ser 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-val830met (accessed [today's date]).

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