Is SARS2 p.Arg232= (c.696C>T) pathogenic?

SARS2 p.Arg232= (c.696C>T) is classified Benign/Likely benign in SARS2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-14). Rare (popmax 0.301%, afr); Associated with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome.

What condition is associated with SARS2 p.Arg232= (c.696C>T)?

SARS2 p.Arg232= (c.696C>T) is associated with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (ClinVar).

How common is SARS2 p.Arg232= (c.696C>T) in the general population?

SARS2 p.Arg232= (c.696C>T) is rare (popmax 0.301%, afr) (gnomAD).

SARS2 p.Arg232=

Q: How is Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome inherited?

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

c.696C>T · rs35389151 · VCV380990

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.301%, afr)

Conditions

hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.025	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	0.133	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.301% African / African-American · 226/75,036 alleles

Filtering AF 0.269% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.257%

Overall 0.0611% 987/1,614,156 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.301%	332
Remaining individualsnot grpmax-eligible	0.0784%	1,276
European (non-Finnish)	0.0567%	1,764
Admixed American	0.05%	2,001
Middle Eastern	0.033%	3,031
East Asian	0.0201%	4,987
South Asian	0.0022%	45,543

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: SARS2
Protein: p.Arg232=
Coding: c.696C>T
MANE Select: NM_017827
dbSNP: rs35389151
Type: single nucleotide variant
Location: chr19:38919825 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.58 · 6 PDB
Residue 232: a β-strand

Full SARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SARS2 p.Arg232Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
SARS2 p.Arg232His Uncertain significance ★ ⚠ same residue
SARS2 c.759+4T>C Uncertain significance ★★ same condition
SARS2 c.-5C>A Uncertain significance ★★ same condition
SARS2 p.Ala167Val Uncertain significance ★★ ⚠ same condition
SARS2 p.Ala463Val Uncertain significance ★★ ⚠ same condition
SARS2 p.Ala516Ser Uncertain significance ★★ ⚠ same condition
SARS2 p.Ala73Pro 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/sars2-p-arg232 (accessed [today's date]).

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