Is DCDC1 p.Thr69Ala (c.205A>G) pathogenic?

DCDC1 p.Thr69Ala (c.205A>G) is classified Uncertain significance in DCDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.0839); Ultra-rare (popmax 0.032%, nfe).

How common is DCDC1 p.Thr69Ala (c.205A>G) in the general population?

DCDC1 p.Thr69Ala (c.205A>G) is ultra-rare (popmax 0.032%, nfe) (gnomAD).

What do computational predictors say about DCDC1 p.Thr69Ala (c.205A>G)?

AlphaMissense predicts likely benign (score 0.0839) — an in-silico prediction, not a clinical call.

DCDC1 p.Thr69Ala

c.205A>G · rs146440557 · VCV2353587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0839 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0839	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.46	GERP 1, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	13.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% European (non-Finnish) · 378/1,179,976 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0283%

Overall 0.0243% 393/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.032%	3,122
Remaining individualsnot grpmax-eligible	0.0208%	4,806
African / African-American	0.00267%	37,463

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: DCDC1
Protein: p.Thr69Ala
Coding: c.205A>G
MANE Select: NM_001387274
dbSNP: rs146440557
Type: single nucleotide variant
Location: chr11:31307868 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.53

Full DCDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC1 p.Gln95His Uncertain significance ★★ ⚠ same type
DCDC1 p.Thr239Met Uncertain significance ★★ ⚠ same type
DCDC1 p.Thr317Ala Uncertain significance ★★ ⚠ same type
DCDC1 c.591+13C>T Benign ★★ same type
DCDC1 p.Ala1431Thr Benign ★★ ⚠ same type
DCDC1 p.Glu200= Benign ★★ same type
DCDC1 p.Leu224= Benign ★★ same type
DCDC1 p.Lys1494Arg Benign ★★ 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/dcdc1-p-thr69ala (accessed [today's date]).

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