Is SHPRH p.Val97= (c.291A>G) pathogenic?

SHPRH p.Val97= (c.291A>G) is classified Likely benign in SHPRH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Ultra-rare (popmax 0.0462%, nfe).

How common is SHPRH p.Val97= (c.291A>G) in the general population?

SHPRH p.Val97= (c.291A>G) is ultra-rare (popmax 0.0462%, nfe) (gnomAD).

SHPRH p.Val97=

c.291A>G · rs199803327 · VCV2656968

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, nfe)

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 -0.92	GERP -2.9
Overall
CADD	1.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0462% European (non-Finnish) · 545/1,179,914 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0416%

Overall 0.0364% 587/1,613,250 alleles · ultra-rare exomes 550/1,461,116 · genomes 37/152,134 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0462%	2,165
Remaining individualsnot grpmax-eligible	0.0352%	2,839
Finnishnot grpmax-eligible	0.0189%	5,287
Admixed American	0.01%	9,996
African / African-American	0.00267%	37,449

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: SHPRH
Protein: p.Val97=
Coding: c.291A>G
MANE Select: NM_001042683
dbSNP: rs199803327
Type: single nucleotide variant
Location: chr6:145955032 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 2 PDB

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

Similar variants

SHPRH p.Ala1099Val Uncertain significance ★ ⚠ same type
SHPRH p.Ala1344Ser Uncertain significance ★ ⚠ same type
SHPRH p.Ala1351Thr Uncertain significance ★ ⚠ same type
SHPRH p.Ala1658Ser Uncertain significance ★ ⚠ same type
SHPRH p.Ala52Thr Uncertain significance ★ ⚠ same type
SHPRH p.Ala66Ser Uncertain significance ★ ⚠ same type
SHPRH p.Ala904Thr Uncertain significance ★ ⚠ same type
SHPRH p.Arg1052His 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/shprh-p-val97 (accessed [today's date]).

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