Is SAMHD1 p.Val91Ile (c.271G>A) pathogenic?

SAMHD1 p.Val91Ile (c.271G>A) is classified Likely benign in SAMHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0771); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SAMHD1 p.Val91Ile (c.271G>A)?

SAMHD1 p.Val91Ile (c.271G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SAMHD1 p.Val91Ile (c.271G>A) in the general population?

SAMHD1 p.Val91Ile (c.271G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAMHD1 p.Val91Ile (c.271G>A)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

SAMHD1 p.Val91Ile

c.271G>A · VCV4630183

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -8.58	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 -0.46	GERP -3.1, phastCons 0.052
Regional constraint	o/e 0.85	unconstrained · MANE · 59 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	12.23	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: SAMHD1
Protein: p.Val91Ile
Coding: c.271G>A
MANE Select: NM_015474
Type: single nucleotide variant
Location: chr20:36946742 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.45 · 76 PDB
Residue 91: the sam domain

Full SAMHD1 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

SAMHD1 p.Val91= Likely benign ★ same residue
SAMHD1 p.Arg145Pro Likely pathogenic ★★ same condition
SAMHD1 p.Arg106Leu Uncertain significance ★★ ⚠ same condition
SAMHD1 p.Arg56His Uncertain significance ★★ ⚠ same condition
SAMHD1 p.Cys554Tyr Uncertain significance ★★ same condition
SAMHD1 p.Glu242Asp Uncertain significance ★★ ⚠ same condition
SAMHD1 p.Glu277Asp Uncertain significance ★★ ⚠ same condition
SAMHD1 p.Gly35Val 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/samhd1-p-val91ile (accessed [today's date]).

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