Is DCN p.Pro315His (c.944C>A) pathogenic?

DCN p.Pro315His (c.944C>A) is classified Likely benign in DCN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.122); Very rare (popmax 0.00254%, nfe); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Pro315His (c.944C>A)?

DCN p.Pro315His (c.944C>A) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Pro315His (c.944C>A) in the general population?

DCN p.Pro315His (c.944C>A) is very rare (popmax 0.00254%, nfe) (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.Pro315His (c.944C>A)?

AlphaMissense predicts likely benign (score 0.122) — an in-silico prediction, not a clinical call.

DCN p.Pro315His

c.944C>A · rs777270608 · VCV310653

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.122	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -9.38	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 0.85, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	21.3	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 0.00254% European (non-Finnish) · 30/1,179,622 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00198% 32/1,613,402 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00313%	31,999
European (non-Finnish)grpmax	0.00254%	39,321

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: DCN
Protein: p.Pro315His
Coding: c.944C>A
MANE Select: NM_001920
dbSNP: rs777270608
Type: single nucleotide variant
Location: chr12:91146194 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 88.60
Residue 315: a disulfide bond

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

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DCN p.Ala11= Benign ★★ same condition
DCN p.Arg235= Benign ★★ same condition
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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-pro315his (accessed [today's date]).

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