Is DCC p.His237Tyr (c.709C>T) pathogenic?

DCC p.His237Tyr (c.709C>T) is classified Benign in DCC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-21). AlphaMissense: likely benign (0.1475); Low-frequency (popmax 1%, sas); Associated with DCC-related disorder.

What condition is associated with DCC p.His237Tyr (c.709C>T)?

DCC p.His237Tyr (c.709C>T) is associated with DCC-related disorder (ClinVar).

How common is DCC p.His237Tyr (c.709C>T) in the general population?

DCC p.His237Tyr (c.709C>T) is low-frequency (popmax 1%, sas) (gnomAD).

What do computational predictors say about DCC p.His237Tyr (c.709C>T)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

DCC p.His237Tyr

c.709C>T · rs201234438 · VCV3052273

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DCC-related disorder

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	22.5	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% South Asian · 911/90,902 alleles

Filtering AF 0.948% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.927%

Overall 0.0604% 970/1,606,710 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1%	100
Remaining individualsnot grpmax-eligible	0.0739%	1,353
Middle Eastern	0.0165%	6,048
East Asian	0.0112%	8,962
Admixed American	0.00167%	59,902
African / African-American	0.00134%	74,848
European (non-Finnish)	0.000426%	234,701

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.His237Tyr
Coding: c.709C>T
MANE Select: NM_005215
dbSNP: rs201234438
Type: single nucleotide variant
Location: chr18:52923718 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 237: the ig-like c2-type 3 domain

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

Disease context

DCC-related disorder

Similar variants

DCC p.His237Asn Uncertain significance ★ ⚠ same residue
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

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-his237tyr (accessed [today's date]).

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