What condition is associated with NFASC p.Pro1008= (c.3024T>C)?

NFASC p.Pro1008= (c.3024T>C) is associated with neurodevelopmental disorder with central and peripheral motor dysfunction (ClinVar).

NFASC p.Pro1008=

Q: Is NFASC p.Pro1008= (c.3024T>C) pathogenic?

NFASC p.Pro1008= (c.3024T>C) is classified Benign in NFASC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-09-05). Common (popmax 30.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with central and peripheral motor dysfunction.

Q: How common is NFASC p.Pro1008= (c.3024T>C) in the general population?

NFASC p.Pro1008= (c.3024T>C) is common (popmax 30.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3024T>C · rs4951151 · VCV1233783

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 30.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

neurodevelopmental disorder with central and peripheral motor dysfunction

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -4.9
Overall
CADD	2.264	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.1% South Asian · 26,921/89,326 alleles

Filtering AF 29.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.7%

Overall 25% 398,999/1,597,614 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	30.1%	3
Middle Eastern	27.2%	4
European (non-Finnish)	25.5%	4
Finnishnot grpmax-eligible	25.4%	4
Remaining individualsnot grpmax-eligible	24.9%	4
Ashkenazi Jewishnot grpmax-eligible	22.7%	4
East Asian	22.1%	5
Amishnot grpmax-eligible	20%	5
Admixed American	19.3%	5
African / African-American	17.4%	6

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.Pro1008=
Coding: c.3024T>C
MANE Select: NM_001005388
dbSNP: rs4951151
Type: single nucleotide variant
Location: chr1:205001174 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 1008: the fibronectin type-iii 4 domain; a UniProt-annotated variant site (in nedcpmd; uncertain significance; no protein expression)

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

Disease context

neurodevelopmental disorder with central and peripheral motor dysfunction — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NFASC c.2593+5G>A Uncertain significance ★★ same condition
NFASC p.Arg436Gln Uncertain significance ★★ same condition
NFASC p.Asn655Asp Uncertain significance ★★ same condition
NFASC p.Val532Leu Uncertain significance ★★ same condition
NFASC c.1280-22A>T Benign ★★ same condition
NFASC c.215+14A>G Benign ★★ same condition
NFASC p.Val518= Benign ★★ same condition
NFASC p.Arg800Ter Likely pathogenic ★ 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-pro1008 (accessed [today's date]).

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