Is AGPS p.Arg317Cys (c.949C>T) pathogenic?

AGPS p.Arg317Cys (c.949C>T) is classified Uncertain significance in AGPS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely pathogenic (0.826); Very rare (popmax 0.00348%, nfe).

How common is AGPS p.Arg317Cys (c.949C>T) in the general population?

AGPS p.Arg317Cys (c.949C>T) is very rare (popmax 0.00348%, nfe) (gnomAD).

What do computational predictors say about AGPS p.Arg317Cys (c.949C>T)?

AlphaMissense predicts likely pathogenic (score 0.826) — an in-silico prediction, not a clinical call.

AGPS p.Arg317Cys

c.949C>T · rs375775258 · VCV1402231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00348%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.826	likely pathogenic
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -9.01	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 145 kb · p 9.9e-28 · regional, not allelic
Overall
CADD	33.0	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 0.00348% European (non-Finnish) · 41/1,179,052 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00267% 43/1,612,288 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00348%	28,757
African / African-American	0.00134%	74,786
South Asian	0.0011%	91,028

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: AGPS
Protein: p.Arg317Cys
Coding: c.949C>T
MANE Select: NM_003659
dbSNP: rs375775258
Type: single nucleotide variant
Location: chr2:177461971 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27
Residue 317: a binding site; the fad-binding pcmh-type domain

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

Similar variants

AGPS p.Arg317= Likely benign ★ same residue
AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same type
AGPS p.Thr309Ile Likely pathogenic ★★ same type
AGPS c.1855+6C>A Uncertain significance ★★ same type
AGPS c.*118A>G Uncertain significance ★★ same type
AGPS p.Arg265Gln Uncertain significance ★★ ⚠ same type
AGPS p.Asn649Ser Uncertain significance ★★ ⚠ same type
AGPS p.Asp28Val 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/agps-p-arg317cys (accessed [today's date]).

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