Is NFASC p.Ser271= (c.813C>T) pathogenic?

NFASC p.Ser271= (c.813C>T) is classified Likely benign in NFASC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-07). Ultra-rare (popmax 0.0113%, nfe); Associated with NFASC-related disorder.

What condition is associated with NFASC p.Ser271= (c.813C>T)?

NFASC p.Ser271= (c.813C>T) is associated with NFASC-related disorder (ClinVar).

How common is NFASC p.Ser271= (c.813C>T) in the general population?

NFASC p.Ser271= (c.813C>T) is ultra-rare (popmax 0.0113%, nfe) (gnomAD).

NFASC p.Ser271=

c.813C>T · rs140997318 · VCV3045816

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, nfe)

Conditions

NFASC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.437	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.8
Overall
CADD	3.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0113% European (non-Finnish) · 133/1,179,166 alleles

Filtering AF 0.0097% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00906%

Overall 0.00911% 147/1,613,092 alleles · ultra-rare exomes 137/1,460,906 · genomes 10/152,186 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,805
European (non-Finnish)grpmax	0.0113%	8,866
South Asian	0.00329%	30,355
East Asian	0.00223%	44,892
Finnishnot grpmax-eligible	0.00156%	64,026
African / African-American	0.00133%	74,910

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.Ser271=
Coding: c.813C>T
MANE Select: NM_001005388
dbSNP: rs140997318
Type: single nucleotide variant
Location: chr1:204968355 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 271: the ig-like c2-type 3 domain

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

Disease context

NFASC-related disorder

Similar variants

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
NFASC p.Ala986= Likely 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-ser271 (accessed [today's date]).

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