Is DCTD p.Ala85= (c.255G>C) pathogenic?

DCTD p.Ala85= (c.255G>C) is classified Benign in DCTD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-30). Common (popmax 5.4%, afr) — too common for a highly-penetrant pathogenic allele.

DCTD p.Ala85=

Q: How common is DCTD p.Ala85= (c.255G>C) in the general population?

DCTD p.Ala85= (c.255G>C) is common (popmax 5.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.255G>C · rs6552619 · VCV776032

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.4%, afr) — too common for a highly-penetrant pathogenic allele

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 -5.4	GERP -4.7
Overall
CADD	0.593	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.4% African / African-American · 4,043/74,914 alleles

Filtering AF 5.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.2%

Overall 0.284% 4,583/1,611,674 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.4%	19
Admixed American	0.372%	269
Remaining individualsnot grpmax-eligible	0.359%	279
Middle Eastern	0.165%	606
South Asian	0.0242%	4,138
European (non-Finnish)	0.00518%	19,308

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: DCTD
Protein: p.Ala85=
Coding: c.255G>C
MANE Select: NM_001921
dbSNP: rs6552619
Type: single nucleotide variant
Location: chr4:182894595 (GRCh38)
Gene constraint: LOEUF 1.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1 PDB
Residue 85: the cmp/dcmp-type deaminase domain; an α-helix

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

Similar variants

DCTD p.Ala23Gly Uncertain significance ★ ⚠ same type
DCTD p.Ala39Thr Uncertain significance ★ ⚠ same type
DCTD p.Arg153Trp Uncertain significance ★ ⚠ same type
DCTD p.Asn54Ser Uncertain significance ★ ⚠ same type
DCTD p.Asp76Val Uncertain significance ★ ⚠ same type
DCTD p.Asp97Glu Uncertain significance ★ ⚠ same type
DCTD p.Cys40Tyr Uncertain significance ★ ⚠ same type
DCTD p.Glu137Lys Uncertain significance ★ ⚠ same type

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/dctd-p-ala85 (accessed [today's date]).

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