Is NFASC p.Ser820= (c.2460C>T) pathogenic?

NFASC p.Ser820= (c.2460C>T) is classified Benign in NFASC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). Common (popmax 7.49%, mid) — too common for a highly-penetrant pathogenic allele; Associated with NFASC-related disorder.

What condition is associated with NFASC p.Ser820= (c.2460C>T)?

NFASC p.Ser820= (c.2460C>T) is associated with NFASC-related disorder (ClinVar).

NFASC p.Ser820=

Q: How common is NFASC p.Ser820= (c.2460C>T) in the general population?

NFASC p.Ser820= (c.2460C>T) is common (popmax 7.49%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2460C>T · rs61741829 · VCV3037774

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.49%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

NFASC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.236	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -5
Overall
CADD	0.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.49% Middle Eastern · 440/5,874 alleles

Filtering AF 6.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.69%

Overall 2.77% 43,473/1,570,408 alleles · common exomes 40,432/1,418,152 · genomes 3,041/152,256 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	7.49%	13
South Asian	5.45%	18
Ashkenazi Jewishnot grpmax-eligible	3.74%	27
Remaining individualsnot grpmax-eligible	2.89%	35
European (non-Finnish)	2.88%	35
Admixed American	1.86%	54
Finnishnot grpmax-eligible	1.3%	77
Amishnot grpmax-eligible	0.658%	152
African / African-American	0.573%	175
East Asian	0.1%	995

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.Ser820=
Coding: c.2460C>T
MANE Select: NM_001005388
dbSNP: rs61741829
Type: single nucleotide variant
Location: chr1:204982010 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 820: the fibronectin type-iii 2 domain

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

Disease context

NFASC-related disorder

Similar variants

NFASC p.Ser820Pro Pathogenic same residue
NFASC c.1831+11A>G Benign same condition
NFASC c.2470+2131G>A Likely benign same condition
NFASC c.3020-9G>A Likely benign same condition
NFASC c.3290-9C>T Likely benign same condition
NFASC c.536-4A>G Likely benign same condition
NFASC c.*1C>T Likely benign same condition
NFASC p.Ala1103= Benign 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-ser820 (accessed [today's date]).

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