Is DCN p.Val306Ala (c.917T>C) pathogenic?

DCN p.Val306Ala (c.917T>C) is classified Benign in DCN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0506); Low-frequency (popmax 1.57%, afr); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Val306Ala (c.917T>C)?

DCN p.Val306Ala (c.917T>C) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Val306Ala (c.917T>C) in the general population?

DCN p.Val306Ala (c.917T>C) is low-frequency (popmax 1.57%, afr) (gnomAD).

How is Congenital stromal corneal dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DCN p.Val306Ala (c.917T>C)?

AlphaMissense predicts likely benign (score 0.0506) — an in-silico prediction, not a clinical call.

DCN p.Val306Ala

c.917T>C · rs73358055 · VCV310654

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0506 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0506	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -4.56	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 -1.3	GERP -4
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	0.74	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 1.57% African / African-American · 1,174/74,950 alleles

Filtering AF 1.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.46%

Overall 0.0805% 1,297/1,611,946 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.57%	64
Remaining individualsnot grpmax-eligible	0.0913%	1,096
Admixed American	0.0867%	1,153
Middle Eastern	0.0165%	6,058
South Asian	0.0011%	90,912
European (non-Finnish)	0.00102%	98,186

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: DCN
Protein: p.Val306Ala
Coding: c.917T>C
MANE Select: NM_001920
dbSNP: rs73358055
Type: single nucleotide variant
Location: chr12:91146221 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 88.60

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

Disease context

congenital stromal corneal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital stromal corneal dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Neonatal

Similar variants

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DCN c.*160C>T Benign ★★ same condition
DCN c.*51A>G Benign ★★ same condition
DCN p.Ala11= Benign ★★ same condition
DCN p.Arg235= Benign ★★ same condition
DCN p.Ile177Phe Benign ★★ ⚠ same condition
DCN p.Lys142Glu Benign ★★ ⚠ 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/dcn-p-val306ala (accessed [today's date]).

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