Is ASPNAT p.Arg116His (c.347G>A) pathogenic?

ASPNAT p.Arg116His (c.347G>A) is classified Uncertain significance in ASPNAT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-26). AlphaMissense: likely benign (0.1325); Very rare (popmax 0.00306%, afr).

How common is ASPNAT p.Arg116His (c.347G>A) in the general population?

ASPNAT p.Arg116His (c.347G>A) is very rare (popmax 0.00306%, afr) (gnomAD).

What do computational predictors say about ASPNAT p.Arg116His (c.347G>A)?

AlphaMissense predicts likely benign (score 0.1325) — an in-silico prediction, not a clinical call.

ASPNAT p.Arg116His

c.347G>A · rs1358478161 · VCV2594565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1325 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00306%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1325	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.55	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 4.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,534 bp · p 0.84 · regional, not allelic
Overall
CADD	23.2	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 0.00306% African / African-American · 2/65,436 alleles

Filtering AF 0.00056% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000409%

Overall 0.000944% 13/1,376,458 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00306%	32,718
European (non-Finnish)	0.00104%	95,831

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: ASPNAT
Protein: p.Arg116His
Coding: c.347G>A
MANE Select: NM_178557
dbSNP: rs1358478161
Type: single nucleotide variant
Location: chr4:2059858 (GRCh38)
Structure: AlphaFold pLDDT 81.36

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

Similar variants

ASPNAT c.541+8C>T Benign ★★ same type
ASPNAT p.Ala35= Likely benign ★★ same type
ASPNAT p.Gly263= Likely benign ★★ same type
ASPNAT p.Pro56= Likely benign ★★ same type
ASPNAT p.Ala125Thr Uncertain significance ★ ⚠ same type
ASPNAT p.Ala225Thr Uncertain significance ★ ⚠ same type
ASPNAT p.Ala22Val Uncertain significance ★ ⚠ same type
ASPNAT p.Ala255Thr 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/aspnat-p-arg116his (accessed [today's date]).

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