Is HS6ST2 p.Pro191Arg (c.572C>G) pathogenic?

HS6ST2 p.Pro191Arg (c.572C>G) is classified Likely benign in HS6ST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1042); Rare (popmax 0.161%, mid).

How common is HS6ST2 p.Pro191Arg (c.572C>G) in the general population?

HS6ST2 p.Pro191Arg (c.572C>G) is rare (popmax 0.161%, mid) (gnomAD).

What do computational predictors say about HS6ST2 p.Pro191Arg (c.572C>G)?

AlphaMissense predicts likely benign (score 0.1042) — an in-silico prediction, not a clinical call.

HS6ST2 p.Pro191Arg

c.572C>G · rs1245417639 · VCV2492874

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1042 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.161%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1042	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 0.64, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 330 kb · p 0.16 · regional, not allelic
Overall
CADD	18.98	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.161% Middle Eastern · 7/4,350 alleles

Filtering AF 0.0754% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0535%

Overall 0.000826% 10/1,210,048 alleles · rare exomes 9/1,097,598 · genomes 1/112,450 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.161%	621
Remaining individualsnot grpmax-eligible	0.0021%	47,600
European (non-Finnish)	0.000223%	447,525

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: HS6ST2
Protein: p.Pro191Arg
Coding: c.572C>G
MANE Select: NM_001394073
dbSNP: rs1245417639
Type: single nucleotide variant
Location: chrX:132957183 (GRCh38)
Structure: AlphaFold pLDDT 74.28

Full HS6ST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HS6ST2 p.Arg9Trp Uncertain significance ★★ ⚠ same type
HS6ST2 p.Gly306Ala Uncertain significance ★★ ⚠ same type
HS6ST2 p.Lys218Gln Uncertain significance ★★ ⚠ same type
HS6ST2 p.Pro581Leu Uncertain significance ★★ ⚠ same type
HS6ST2 p.Ala325= Benign/Likely benign ★★ same type
HS6ST2 p.Arg51Leu Benign ★★ same type
HS6ST2 p.Leu107= Benign ★★ same type
HS6ST2 p.Ala202Ser Uncertain significance ★ ⚠ same type

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/hs6st2-p-pro191arg (accessed [today's date]).

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