Is SBDS p.Ser55Ter (c.164C>G) pathogenic?

SBDS p.Ser55Ter (c.164C>G) is classified Likely pathogenic in SBDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-20). Very rare (popmax 0.00133%, afr); Associated with SBDS-related disorder.

What condition is associated with SBDS p.Ser55Ter (c.164C>G)?

SBDS p.Ser55Ter (c.164C>G) is associated with SBDS-related disorder, aplastic anemia (ClinVar).

How common is SBDS p.Ser55Ter (c.164C>G) in the general population?

SBDS p.Ser55Ter (c.164C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

SBDS p.Ser55Ter

c.164C>G · rs369175778 · VCV3240424

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

SBDS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Pangolin	Δ0.44	loss · gain 0.30 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,872 alleles · very rare exomes 3/1,461,708 · genomes 4/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.000509%	196,650

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: SBDS
Protein: p.Ser55Ter
Coding: c.164C>G
MANE Select: NM_016038
dbSNP: rs369175778
Type: single nucleotide variant
Location: chr7:66994306 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 6 PDB
Residue 55: a β-strand

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

Disease context

SBDS-related disorder

Also linked: aplastic anemia

Similar variants

SBDS p.Ser55Thr Uncertain significance ★ ⚠ same residue
SBDS p.Ser55= Likely benign ★ same residue
SBDS c.258+1G>C Pathogenic ★★ same condition
SBDS c.258+2T>C Pathogenic/Likely pathogenic ★★ same condition
SBDS c.624+1G>A Likely pathogenic ★★ same condition
SBDS p.Arg218Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SBDS p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
SBDS p.Lys33Thr 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/sbds-p-ser55ter (accessed [today's date]).

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