Is NFASC p.Pro382Arg (c.1145C>G) pathogenic?

NFASC p.Pro382Arg (c.1145C>G) is classified Uncertain significance in NFASC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with NFASC p.Pro382Arg (c.1145C>G)?

NFASC p.Pro382Arg (c.1145C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NFASC p.Pro382Arg (c.1145C>G) in the general population?

NFASC p.Pro382Arg (c.1145C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

NFASC p.Pro382Arg

c.1145C>G · VCV3405062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.097	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP -0.15, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 53 kb · p 8.7e-18 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,952 alleles

Overall 0.000124% 2/1,614,080 alleles · very rare exomes 1/1,461,824 · genomes 1/152,256 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00133%	74,952

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NFASC
Protein: p.Pro382Arg
Coding: c.1145C>G
MANE Select: NM_001005388
Type: single nucleotide variant
Location: chr1:204973285 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 382: the ig-like c2-type 4 domain

Full NFASC 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

NFASC p.Ala253Thr Uncertain significance ★★ same condition
NFASC p.Arg133His Uncertain significance ★★ same condition
NFASC p.Asp1038Ala Uncertain significance ★★ same condition
NFASC p.Asp601Val Uncertain significance ★★ same condition
NFASC p.Gly23Arg Uncertain significance ★★ same condition
NFASC p.Leu287Phe Uncertain significance ★★ same condition
NFASC p.Thr973Ala Uncertain significance ★★ same condition
NFASC p.Val532Leu 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/nfasc-p-pro382arg (accessed [today's date]).

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