Is SARS2 p.Val192= (c.576C>T) pathogenic?

SARS2 p.Val192= (c.576C>T) is classified Benign/Likely benign in SARS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-12). Rare (popmax 0.172%, afr); Associated with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome.

What condition is associated with SARS2 p.Val192= (c.576C>T)?

SARS2 p.Val192= (c.576C>T) is associated with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (ClinVar).

How common is SARS2 p.Val192= (c.576C>T) in the general population?

SARS2 p.Val192= (c.576C>T) is rare (popmax 0.172%, afr) (gnomAD).

SARS2 p.Val192=

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.576C>T · rs150249937 · VCV378497

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, 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.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.67 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.3	GERP -4.4
Overall
CADD	6.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% African / African-American · 129/75,032 alleles

Filtering AF 0.148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.00905% 146/1,613,540 alleles · rare exomes 79/1,461,296 · genomes 67/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.172%	582
Remaining individualsnot grpmax-eligible	0.0112%	8,923
Admixed American	0.00333%	30,001
East Asian	0.00223%	44,886
European (non-Finnish)	0.000593%	168,563

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.Val192=
Coding: c.576C>T
MANE Select: NM_017827
dbSNP: rs150249937
Type: single nucleotide variant
Location: chr19:38921405 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.58 · 6 PDB
Residue 192: 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 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-val192 (accessed [today's date]).

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