Is FUCA1 p.Pro413Arg (c.1238C>G) pathogenic?

FUCA1 p.Pro413Arg (c.1238C>G) is classified Uncertain significance in FUCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely pathogenic (0.8338); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FUCA1 p.Pro413Arg (c.1238C>G)?

FUCA1 p.Pro413Arg (c.1238C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FUCA1 p.Pro413Arg (c.1238C>G) in the general population?

FUCA1 p.Pro413Arg (c.1238C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FUCA1 p.Pro413Arg (c.1238C>G)?

AlphaMissense predicts likely pathogenic (score 0.8338) — an in-silico prediction, not a clinical call.

FUCA1 p.Pro413Arg

c.1238C>G · VCV3517712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8338	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -17.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.31 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: FUCA1
Protein: p.Pro413Arg
Coding: c.1238C>G
MANE Select: NM_000147
Type: single nucleotide variant
Location: chr1:23846096 (GRCh38)
Gene constraint: LOEUF 1.162 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.60 · 2 PDB

Full FUCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FUCA1 p.Pro413Ser Uncertain significance ★★ ⚠ same residue
FUCA1 p.Ala368Thr Uncertain significance ★★ ⚠ same condition
FUCA1 p.Arg162Gln Uncertain significance ★★ ⚠ same condition
FUCA1 p.Arg162Trp Uncertain significance ★★ ⚠ same condition
FUCA1 p.Arg173Gln Uncertain significance ★★ ⚠ same condition
FUCA1 p.Arg178His Uncertain significance ★★ ⚠ same condition
FUCA1 p.Arg30Trp Uncertain significance ★★ ⚠ same condition
FUCA1 p.Arg9Trp Uncertain significance ★★ ⚠ 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/fuca1-p-pro413arg (accessed [today's date]).

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