Is SARS2 p.Arg15Pro (c.44G>C) pathogenic?

SARS2 p.Arg15Pro (c.44G>C) is classified Uncertain significance in SARS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-12). AlphaMissense: likely benign (0.0927); Ultra-rare (popmax 0.0317%, amr); Associated with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome.

What condition is associated with SARS2 p.Arg15Pro (c.44G>C)?

SARS2 p.Arg15Pro (c.44G>C) is associated with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (ClinVar).

How common is SARS2 p.Arg15Pro (c.44G>C) in the general population?

SARS2 p.Arg15Pro (c.44G>C) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about SARS2 p.Arg15Pro (c.44G>C)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

SARS2 p.Arg15Pro

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.44G>C · rs773524954 · VCV329226

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -2.8
Regional constraint	o/e 0.95	unconstrained · MANE · 15 kb · p 0.21 · regional, not allelic
Overall
CADD	8.56	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 0.0317% Admixed American · 19/60,010 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00508% 82/1,613,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,158
European (non-Finnish)	0.00534%	18,731

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.Arg15Pro
Coding: c.44G>C
MANE Select: NM_017827
dbSNP: rs773524954
Type: single nucleotide variant
Location: chr19:38930693 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.58 · 6 PDB

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 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
SARS2 p.Arg118Gln Uncertain significance ★★ ⚠ same condition
SARS2 p.Arg139Trp 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-arg15pro (accessed [today's date]).

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