Is DCDC2C p.Tyr21Cys (c.62A>G) pathogenic?

DCDC2C p.Tyr21Cys (c.62A>G) is classified Likely benign in DCDC2C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). AlphaMissense: likely pathogenic (0.7517); Low-frequency (popmax 1.1%, nfe).

How common is DCDC2C p.Tyr21Cys (c.62A>G) in the general population?

DCDC2C p.Tyr21Cys (c.62A>G) is low-frequency (popmax 1.1%, nfe) (gnomAD).

What do computational predictors say about DCDC2C p.Tyr21Cys (c.62A>G)?

AlphaMissense predicts likely pathogenic (score 0.7517) — an in-silico prediction, not a clinical call.

DCDC2C p.Tyr21Cys

c.62A>G · rs142564019 · VCV2650638

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7517 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.7517	likely pathogenic
SaProt	LLR -14.17	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.086, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 143 kb · p 0.31 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.1% European (non-Finnish) · 10,969/998,352 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 0.956% 12,033/1,259,240 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.28%	78
European (non-Finnish)grpmax	1.1%	91
Remaining individualsnot grpmax-eligible	0.703%	142
Admixed American	0.358%	280
Middle Eastern	0.216%	463
African / African-American	0.167%	598
Ashkenazi Jewishnot grpmax-eligible	0.0772%	1,296
South Asian	0.065%	1,539

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DCDC2C
Protein: p.Tyr21Cys
Coding: c.62A>G
MANE Select: NM_001287444
dbSNP: rs142564019
Type: single nucleotide variant
Location: chr2:3703813 (GRCh38)
Gene constraint: LOEUF 1.498 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.53
Residue 21: the doublecortin 1 domain

Full DCDC2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC2C c.955-1G>C Uncertain significance ★ same type
DCDC2C p.Ala301= Likely 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/dcdc2c-p-tyr21cys (accessed [today's date]).

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