Is BCS1L p.Asp57= (c.171C>T) pathogenic?

BCS1L p.Asp57= (c.171C>T) is classified Conflicting classifications of pathogenicity in BCS1L (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-03-26). Very rare (popmax 0.00415%, nfe); Associated with GRACILE syndrome.

What condition is associated with BCS1L p.Asp57= (c.171C>T)?

BCS1L p.Asp57= (c.171C>T) is associated with GRACILE syndrome, mitochondrial complex III deficiency nuclear type 1, Leigh syndrome (ClinVar).

How common is BCS1L p.Asp57= (c.171C>T) in the general population?

BCS1L p.Asp57= (c.171C>T) is very rare (popmax 0.00415%, nfe) (gnomAD).

How is GRACILE syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BCS1L p.Asp57=

c.171C>T · rs756932413 · VCV380986

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Conditions

GRACILE syndrome

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 2.8	GERP 1.4, phastCons 1
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% European (non-Finnish) · 49/1,180,050 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00328% 53/1,614,124 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,083
Finnishnot grpmax-eligible	0.00312%	32,020
Admixed American	0.00167%	60,006
African / African-American	0.00133%	74,940

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: BCS1L
Protein: p.Asp57=
Coding: c.171C>T
MANE Select: NM_001079866
dbSNP: rs756932413
Type: single nucleotide variant
Location: chr2:218661158 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10

Full BCS1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GRACILE syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial complex III deficiency nuclear type 1 Leigh syndrome

For GRACILE syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

BCS1L p.Asp57Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BCS1L c.320+1G>T Pathogenic/Likely pathogenic ★★ same condition
BCS1L c.889+1G>T Pathogenic/Likely pathogenic ★★ same condition
BCS1L c.889+2T>G Likely pathogenic ★★ same condition
BCS1L c.-50+388C>G Likely pathogenic ★★ same condition
BCS1L c.-50+405A>G Pathogenic/Likely pathogenic ★★ same condition
BCS1L p.Arg109Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
BCS1L p.Arg114Trp Pathogenic/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/bcs1l-p-asp57 (accessed [today's date]).

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