Is SAMHD1 p.Asp440= (c.1320C>T) pathogenic?

SAMHD1 p.Asp440= (c.1320C>T) is classified Likely benign in SAMHD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0987%, mid); Associated with Aicardi-Goutieres syndrome 5.

What condition is associated with SAMHD1 p.Asp440= (c.1320C>T)?

SAMHD1 p.Asp440= (c.1320C>T) is associated with Aicardi-Goutieres syndrome 5, Aicardi-Goutieres syndrome (ClinVar).

How common is SAMHD1 p.Asp440= (c.1320C>T) in the general population?

SAMHD1 p.Asp440= (c.1320C>T) is ultra-rare (popmax 0.0987%, mid) (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.Asp440=

c.1320C>T · rs371992324 · VCV785741

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

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 -1.6	GERP -3.4
Overall
CADD	1.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0987% Middle Eastern · 6/6,080 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00626% 101/1,613,090 alleles · ultra-rare exomes 88/1,461,062 · genomes 13/152,028 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,013
African / African-American	0.0174%	5,759
Remaining individualsnot grpmax-eligible	0.0112%	8,923
Admixed American	0.00667%	14,989
European (non-Finnish)	0.00568%	17,602
South Asian	0.00329%	30,354
East Asian	0.00223%	44,868

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.Asp440=
Coding: c.1320C>T
MANE Select: NM_015474
dbSNP: rs371992324
Type: single nucleotide variant
Location: chr20:36905454 (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 440: an α-helix

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

Also linked: Aicardi-Goutieres syndrome

For Aicardi-Goutières syndrome (Orphanet):

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

Similar variants

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
SAMHD1 p.Arg143His 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-asp440 (accessed [today's date]).

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