Is SAMD9 p.Phe705Ser (c.2114T>C) pathogenic?

SAMD9 p.Phe705Ser (c.2114T>C) is classified Uncertain significance in SAMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-22). AlphaMissense: likely pathogenic (0.8268); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SAMD9 p.Phe705Ser (c.2114T>C)?

SAMD9 p.Phe705Ser (c.2114T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9 p.Phe705Ser (c.2114T>C) in the general population?

SAMD9 p.Phe705Ser (c.2114T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAMD9 p.Phe705Ser (c.2114T>C)?

AlphaMissense predicts likely pathogenic (score 0.8268) — an in-silico prediction, not a clinical call.

SAMD9 p.Phe705Ser

c.2114T>C · VCV4863766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8268 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8268	likely pathogenic · top 9% in SAMD9
REVEL	0.284	benign-leaning
SaProt	LLR -11.40	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 1,217 bp · p 1.8e-06 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SAMD9
Protein: p.Phe705Ser
Coding: c.2114T>C
MANE Select: NM_017654
Type: single nucleotide variant
Location: chr7:93103984 (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.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-phe705ser (accessed [today's date]).

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