Is SAMD9 p.Trp14Leu (c.41G>T) pathogenic?

SAMD9 p.Trp14Leu (c.41G>T) is classified Uncertain significance in SAMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-04). AlphaMissense: likely pathogenic (0.7518); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SAMD9 p.Trp14Leu (c.41G>T)?

SAMD9 p.Trp14Leu (c.41G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9 p.Trp14Leu (c.41G>T) in the general population?

SAMD9 p.Trp14Leu (c.41G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAMD9 p.Trp14Leu (c.41G>T)?

AlphaMissense predicts likely pathogenic (score 0.7518) — an in-silico prediction, not a clinical call.

SAMD9 p.Trp14Leu

c.41G>T · VCV3791973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7518 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,592,072)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7518	likely pathogenic
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -14.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 4.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,176 bp · p 0.058 · regional, not allelic
Overall
CADD	24.9	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

No allele count reported in gnomAD v4.1 (AN 1,592,072). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SAMD9
Protein: p.Trp14Leu
Coding: c.41G>T
MANE Select: NM_017654
Type: single nucleotide variant
Location: chr7:93106057 (GRCh38)
Gene constraint: LOEUF 1.773 · pLI 0.03 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.79 · 10 PDB
Residue 14: the sam domain

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.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
SAMD9 p.Ala1290Val 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-trp14leu (accessed [today's date]).

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