Is RNASEH2A p.Pro173= (c.519G>A) pathogenic?

RNASEH2A p.Pro173= (c.519G>A) is classified Likely benign in RNASEH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). Very rare (popmax 0.004%, afr); Associated with Aicardi-Goutieres syndrome 4.

What condition is associated with RNASEH2A p.Pro173= (c.519G>A)?

RNASEH2A p.Pro173= (c.519G>A) is associated with Aicardi-Goutieres syndrome 4 (ClinVar).

How common is RNASEH2A p.Pro173= (c.519G>A) in the general population?

RNASEH2A p.Pro173= (c.519G>A) is very rare (popmax 0.004%, afr) (gnomAD).

How is Aicardi-Goutières syndrome inherited?

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

RNASEH2A p.Pro173=

c.519G>A · rs761321776 · VCV2793608

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Aicardi-Goutieres syndrome 4

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 -12	GERP -3.1
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,938 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00062% 10/1,614,088 alleles · very rare exomes 9/1,461,892 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,979
South Asian	0.0022%	45,542
European (non-Finnish)	0.000424%	236,008

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: RNASEH2A
Protein: p.Pro173=
Coding: c.519G>A
MANE Select: NM_006397
dbSNP: rs761321776
Type: single nucleotide variant
Location: chr19:12810178 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.69 · 3 PDB
Residue 173: the rnase h type-2 domain; an α-helix

Full RNASEH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Aicardi-Goutieres syndrome 4 — 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

RNASEH2A p.Pro173Leu Uncertain significance ★★ ⚠ same residue
RNASEH2A c.199+1G>C Likely pathogenic ★★ same condition
RNASEH2A p.Arg186Gln Pathogenic/Likely pathogenic ★★ same condition
RNASEH2A p.Arg186Trp Pathogenic/Likely pathogenic ★★ same condition
RNASEH2A p.Arg235Gln Likely pathogenic ★★ same condition
RNASEH2A p.Trp219Ter Pathogenic/Likely pathogenic ★★ same condition
RNASEH2A c.411+3G>C Uncertain significance ★★ same condition
RNASEH2A p.Ala121Thr 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/rnaseh2a-p-pro173 (accessed [today's date]).

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