Is ARGFX p.Thr283Pro (c.847A>C) pathogenic?

ARGFX p.Thr283Pro (c.847A>C) is classified Uncertain significance in ARGFX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). AlphaMissense: likely benign (0.0925); Absent from gnomAD v4.1.

How common is ARGFX p.Thr283Pro (c.847A>C) in the general population?

ARGFX p.Thr283Pro (c.847A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARGFX p.Thr283Pro (c.847A>C)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

ARGFX p.Thr283Pro

c.847A>C · rs1576445849 · VCV2546465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -3.1
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.019 · regional, not allelic
Overall
CADD	16.63	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARGFX
Protein: p.Thr283Pro
Coding: c.847A>C
MANE Select: NM_001012659
dbSNP: rs1576445849
Type: single nucleotide variant
Location: chr3:121586499 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.78

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

Similar variants

ARGFX p.Ala190Glu Uncertain significance ★ ⚠ same type
ARGFX p.Arg114Thr Uncertain significance ★ ⚠ same type
ARGFX p.Arg129Gln Uncertain significance ★ ⚠ same type
ARGFX p.Arg129Trp Uncertain significance ★ same type
ARGFX p.Arg130Gln Uncertain significance ★ same type
ARGFX p.Arg212Met Uncertain significance ★ ⚠ same type
ARGFX p.Arg82His Uncertain significance ★ same type
ARGFX p.Asn188Ile 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/argfx-p-thr283pro (accessed [today's date]).

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