Is PRNP p.Ala117= (c.351A>G) pathogenic?

PRNP p.Ala117= (c.351A>G) is classified Benign/Likely benign in PRNP (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-27). Common (popmax 8.38%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inherited prion disease.

What condition is associated with PRNP p.Ala117= (c.351A>G)?

PRNP p.Ala117= (c.351A>G) is associated with Inherited prion disease, Huntington disease-like 1 (ClinVar).

PRNP p.Ala117=

Q: How common is PRNP p.Ala117= (c.351A>G) in the general population?

PRNP p.Ala117= (c.351A>G) is common (popmax 8.38%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.351A>G · rs8124214 · VCV338650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 8.38%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inherited prion disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8	GERP -3.2
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.38% African / African-American · 6,291/75,032 alleles

Filtering AF 8.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.14%

Overall 3.1% 50,059/1,613,982 alleles · common exomes 43,708/1,461,722 · genomes 6,351/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.38%	12
Amishnot grpmax-eligible	3.85%	26
Middle Eastern	3.56%	28
European (non-Finnish)	3.21%	31
Remaining individualsnot grpmax-eligible	3.05%	33
Ashkenazi Jewishnot grpmax-eligible	2.43%	41
Admixed American	2.02%	50
South Asian	1.44%	69
Finnishnot grpmax-eligible	0.783%	128
East Asian	0.00892%	11,217

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: PRNP
Protein: p.Ala117=
Coding: c.351A>G
MANE Select: NM_000311
dbSNP: rs8124214
Type: single nucleotide variant
Location: chr20:4699571 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB
Residue 117: a UniProt-annotated variant site (linked to development of dementing gerstmann-straussler disease); a turn; the 'interaction with grb2, eri3 and syn1' region

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

Disease context

Inherited prion disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Huntington disease-like 1

Similar variants

PRNP p.Ala117Val Pathogenic ★★ ⚠ same residue
PRNP p.Arg148His Likely pathogenic ★★ ⚠ same condition
PRNP p.Arg208His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRNP p.Asp178Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRNP p.Gln217Arg Likely pathogenic ★★ ⚠ same condition
PRNP p.Glu200Lys Pathogenic ★★ ⚠ same condition
PRNP p.Gly131Val Pathogenic/Likely pathogenic ★★ same condition
PRNP p.Phe198Ser Pathogenic ★★ ⚠ 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/prnp-p-ala117 (accessed [today's date]).

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