Is SAMHD1 p.Pro47Ser (c.139C>T) pathogenic?

SAMHD1 p.Pro47Ser (c.139C>T) is classified Uncertain significance in SAMHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1436); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SAMHD1 p.Pro47Ser (c.139C>T)?

SAMHD1 p.Pro47Ser (c.139C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SAMHD1 p.Pro47Ser (c.139C>T) in the general population?

SAMHD1 p.Pro47Ser (c.139C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SAMHD1 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely benign (score 0.1436) — an in-silico prediction, not a clinical call.

SAMHD1 p.Pro47Ser

c.139C>T · VCV4159483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1436 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1436	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.54	GERP 0.61, phastCons 0.046
Regional constraint	o/e 0.85	unconstrained · MANE · 59 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	17.32	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.2e-05% 1/1,614,206 alleles · very rare exomes 1/1,461,836 · genomes 0/152,370 · joint denominator

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.Pro47Ser
Coding: c.139C>T
MANE Select: NM_015474
Type: single nucleotide variant
Location: chr20:36951505 (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 47: the sam domain; an α-helix

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.Pro47Ala Uncertain significance ★ ⚠ same residue
SAMHD1 p.Pro47= 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

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-pro47ser (accessed [today's date]).

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