Is DCC p.Val621Met (c.1861G>A) pathogenic?

DCC p.Val621Met (c.1861G>A) is classified Likely benign in DCC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-20). AlphaMissense: likely benign (0.313); Rare (popmax 0.22%, afr); Associated with DCC-related disorder.

What condition is associated with DCC p.Val621Met (c.1861G>A)?

DCC p.Val621Met (c.1861G>A) is associated with DCC-related disorder (ClinVar).

How common is DCC p.Val621Met (c.1861G>A) in the general population?

DCC p.Val621Met (c.1861G>A) is rare (popmax 0.22%, afr) (gnomAD).

What do computational predictors say about DCC p.Val621Met (c.1861G>A)?

AlphaMissense predicts likely benign (score 0.313) — an in-silico prediction, not a clinical call.

DCC p.Val621Met

c.1861G>A · rs112302456 · VCV3045915

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.313 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.22%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DCC-related disorder

Computational evidence

Protein change
AlphaMissense	0.313	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -12.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	34.0	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 0.22% African / African-American · 165/74,878 alleles

Filtering AF 0.193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.0142% 229/1,610,296 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.22%	454
Remaining individualsnot grpmax-eligible	0.0433%	2,311
Admixed American	0.0267%	3,750
South Asian	0.0121%	8,274
European (non-Finnish)	0.00085%	117,687

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: DCC
Protein: p.Val621Met
Coding: c.1861G>A
MANE Select: NM_005215
dbSNP: rs112302456
Type: single nucleotide variant
Location: chr18:53207817 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 621: a UniProt-annotated variant site (in mrmv1; likely pathogenic)

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

Disease context

DCC-related disorder

Similar variants

DCC c.2828-1G>A Likely pathogenic ★ same condition
DCC c.3898+2T>C Likely pathogenic ★ same condition
DCC p.Arg501Ter Likely pathogenic ★ same condition
DCC p.Glu512Ter Likely pathogenic ★ same condition
DCC p.Trp508Ter Likely pathogenic ★ same condition
DCC p.Trp745Ter Likely pathogenic ★ same condition
DCC p.Pro1086Leu Uncertain significance ⚠ same condition
DCC p.Thr614Ile 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/dcc-p-val621met (accessed [today's date]).

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