Is NFASC p.Asp341= (c.1023C>T) pathogenic?

NFASC p.Asp341= (c.1023C>T) is classified Benign in NFASC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele.

NFASC p.Asp341=

Q: How common is NFASC p.Asp341= (c.1023C>T) in the general population?

NFASC p.Asp341= (c.1023C>T) is common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1023C>T · rs6690894 · VCV784969

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.544	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -5
Overall
CADD	7.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.56% African / African-American · 4,925/75,022 alleles

Filtering AF 6.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.35%

Overall 0.35% 5,651/1,614,024 alleles · common exomes 2,701/1,461,726 · genomes 2,950/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.56%	15
Admixed American	0.472%	212
Remaining individualsnot grpmax-eligible	0.448%	223
Middle Eastern	0.185%	541
South Asian	0.022%	4,554
European (non-Finnish)	0.0109%	9,148
East Asian	0.00668%	14,963

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.Asp341=
Coding: c.1023C>T
MANE Select: NM_001005388
dbSNP: rs6690894
Type: single nucleotide variant
Location: chr1:204970635 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 341: a β-strand; the ig-like c2-type 4 domain

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

Similar variants

NFASC c.2593+5G>A Uncertain significance ★★ same type
NFASC p.Ala253Thr Uncertain significance ★★ same type
NFASC p.Arg133His Uncertain significance ★★ same type
NFASC p.Arg436Gln Uncertain significance ★★ same type
NFASC p.Asn655Asp Uncertain significance ★★ same type
NFASC p.Asp1038Ala Uncertain significance ★★ same type
NFASC p.Asp601Val Uncertain significance ★★ same type
NFASC p.Gly23Arg 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/nfasc-p-asp341 (accessed [today's date]).

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