Is DCN p.Ile177Phe (c.529A>T) pathogenic?

DCN p.Ile177Phe (c.529A>T) is classified Benign in DCN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-16). AlphaMissense: ambiguous (0.3532); Ultra-rare (popmax 0.027%, nfe); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Ile177Phe (c.529A>T)?

DCN p.Ile177Phe (c.529A>T) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Ile177Phe (c.529A>T) in the general population?

DCN p.Ile177Phe (c.529A>T) is ultra-rare (popmax 0.027%, 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.Ile177Phe (c.529A>T)?

AlphaMissense predicts ambiguous (score 0.3532) — an in-silico prediction, not a clinical call.

DCN p.Ile177Phe

c.529A>T · rs201430261 · VCV310658

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3532 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.3532	ambiguous
REVEL	0.162	moderately benign-leaning
SaProt	LLR -7.56	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	20.5	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 0.027% European (non-Finnish) · 314/1,164,536 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.0223% 356/1,597,200 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0274%	3,646
European (non-Finnish)grpmax	0.027%	3,709
South Asian	0.0198%	5,041
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,741
Admixed American	0.00667%	14,999
Finnishnot grpmax-eligible	0.00156%	64,024

Remaining individuals 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.Ile177Phe
Coding: c.529A>T
MANE Select: NM_001920
dbSNP: rs201430261
Type: single nucleotide variant
Location: chr12:91158305 (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

DCN p.Lys187Arg Uncertain significance ★★ ⚠ same condition
DCN c.212-6T>C Benign ★★ same condition
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.Lys142Glu Benign ★★ ⚠ same condition
DCN p.Pro18= Benign/Likely 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-ile177phe (accessed [today's date]).

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