Is DDOST p.Ala277= (c.831C>T) pathogenic?

DDOST p.Ala277= (c.831C>T) is classified Benign/Likely benign in DDOST (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Common (popmax 7.19%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DDOST-congenital disorder of glycosylation.

What condition is associated with DDOST p.Ala277= (c.831C>T)?

DDOST p.Ala277= (c.831C>T) is associated with DDOST-congenital disorder of glycosylation (ClinVar).

How is DDOST-CDG inherited?

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

DDOST p.Ala277=

Q: How common is DDOST p.Ala277= (c.831C>T) in the general population?

DDOST p.Ala277= (c.831C>T) is common (popmax 7.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.831C>T · rs6692016 · VCV295114

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 7.19%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DDOST-congenital disorder of glycosylation

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 1.3	GERP -1, phastCons 1
Overall
CADD	9.675	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.19% African / African-American · 5,392/74,998 alleles

Filtering AF 7.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.96%

Overall 0.818% 13,198/1,613,924 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.19%	14
South Asian	4.31%	23
East Asian	3.08%	32
Ashkenazi Jewishnot grpmax-eligible	1.59%	63
Remaining individualsnot grpmax-eligible	1.24%	80
Admixed American	0.937%	107
Middle Eastern	0.759%	132
European (non-Finnish)	0.0541%	1,849
Finnishnot grpmax-eligible	0.00313%	31,994

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: DDOST
Protein: p.Ala277=
Coding: c.831C>T
MANE Select: NM_005216
dbSNP: rs6692016
Type: single nucleotide variant
Location: chr1:20653738 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB
Residue 277: a turn

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

Disease context

DDOST-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DDOST-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DDOST p.Gln215His Pathogenic/Likely pathogenic ★★ ⚠ same condition
DDOST c.-18T>G Uncertain significance ★★ ⚠ same condition
DDOST p.Ala11Val Uncertain significance ★★ ⚠ same condition
DDOST p.Ala219Val Uncertain significance ★★ ⚠ same condition
DDOST p.Ala232Ser Uncertain significance ★★ ⚠ same condition
DDOST p.Ala415Thr Uncertain significance ★★ ⚠ same condition
DDOST p.Arg237His Uncertain significance ★★ ⚠ same condition
DDOST p.Arg280Cys Uncertain significance ★★ ⚠ 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/ddost-p-ala277 (accessed [today's date]).

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