Is SAMHD1 p.Phe213fs (c.638_647del) pathogenic?

SAMHD1 p.Phe213fs (c.638647del) is classified Pathogenic in SAMHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-09). No gnomAD frequency available for this variant; Associated with Aicardi-Goutieres syndrome 5.

What condition is associated with SAMHD1 p.Phe213fs (c.638_647del)?

SAMHD1 p.Phe213fs (c.638_647del) is associated with Aicardi-Goutieres syndrome 5 (ClinVar).

How common is SAMHD1 p.Phe213fs (c.638_647del) in the general population?

SAMHD1 p.Phe213fs (c.638_647del) is no gnomAD frequency available for this variant (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.Phe213fs

c.638_647del · rs2146127824 · VCV1410719

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Aicardi-Goutieres syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: SAMHD1
Protein: p.Phe213fs
Coding: c.638_647del
MANE Select: NM_015474
dbSNP: rs2146127824
Type: Deletion
Location: chr20:36927231 (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 213: a turn; the hd domain

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 c.349-6_354del Likely pathogenic ★★ same condition
SAMHD1 p.Ala529fs Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Gln190fs Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Glu479fs Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Ile222fs Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Lys492fs Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Met216fs Pathogenic/Likely pathogenic ★★ same condition
SAMHD1 p.Met505fs 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-phe213fs (accessed [today's date]).

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