Is SAMHD1 p.Ala30= (c.90A>C) pathogenic?

SAMHD1 p.Ala30= (c.90A>C) is classified Likely benign in SAMHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-22). Ultra-rare (popmax 0.0143%, sas); Associated with Aicardi-Goutieres syndrome 5.

What condition is associated with SAMHD1 p.Ala30= (c.90A>C)?

SAMHD1 p.Ala30= (c.90A>C) is associated with Aicardi-Goutieres syndrome 5 (ClinVar).

How common is SAMHD1 p.Ala30= (c.90A>C) in the general population?

SAMHD1 p.Ala30= (c.90A>C) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

How is Aicardi-Goutières syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SAMHD1 p.Ala30=

c.90A>C · rs780812058 · VCV1101844

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Conditions

Aicardi-Goutieres syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -3.2
Overall
CADD	1.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/91,090 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000991% 16/1,614,070 alleles · ultra-rare exomes 15/1,461,842 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,007
East Asian	0.00668%	14,963

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: SAMHD1
Protein: p.Ala30=
Coding: c.90A>C
MANE Select: NM_015474
dbSNP: rs780812058
Type: single nucleotide variant
Location: chr20:36951554 (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 30: the 'disordered' region

Full SAMHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Aicardi-Goutieres syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aicardi-Goutières syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SAMHD1 p.Ala30Ser Uncertain significance ★ ⚠ same residue
SAMHD1 c.1062+1G>T Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 c.1411-2A>G Pathogenic ★★ same condition
SAMHD1 c.509+1G>A Likely pathogenic ★★ same condition
SAMHD1 c.626-1G>C Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Arg106Ter Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Arg134Ter Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Arg143Cys Pathogenic/Likely pathogenic ★★ 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-ala30 (accessed [today's date]).

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