Is CHRDL1 p.Glu69Asp (c.207G>C) pathogenic?

CHRDL1 p.Glu69Asp (c.207G>C) is classified Uncertain significance in CHRDL1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1683); Absent from gnomAD v4.1; Associated with megalocornea.

What condition is associated with CHRDL1 p.Glu69Asp (c.207G>C)?

CHRDL1 p.Glu69Asp (c.207G>C) is associated with megalocornea (ClinVar).

How common is CHRDL1 p.Glu69Asp (c.207G>C) in the general population?

CHRDL1 p.Glu69Asp (c.207G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRDL1 p.Glu69Asp (c.207G>C)?

AlphaMissense predicts likely benign (score 0.1683) — an in-silico prediction, not a clinical call.

CHRDL1 p.Glu69Asp

c.207G>C · rs2148509597 · VCV1077003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1683 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

megalocornea

Computational evidence

Protein change
AlphaMissense	0.1683	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -5.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.81	donor loss · deltas
Pangolin	Δ0.69	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 116 kb · p 0.22 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHRDL1
Protein: p.Glu69Asp
Coding: c.207G>C
MANE Select: NM_001143981
dbSNP: rs2148509597
Type: single nucleotide variant
Location: chrX:110762695 (GRCh38)
Structure: AlphaFold pLDDT 69.79
Residue 69: the vwfc 1 domain

Full CHRDL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

megalocornea — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRDL1 c.1156+1G>T Pathogenic ★ same condition
CHRDL1 c.301+2T>G Pathogenic ★ same condition
CHRDL1 c.94+1G>A Pathogenic ★ same condition
CHRDL1 p.Arg77Ter Pathogenic ★ same condition
CHRDL1 p.Cys146Gly Likely pathogenic ★ same condition
CHRDL1 p.Lys326Ter Pathogenic ★ same condition
CHRDL1 p.Cys323Phe Uncertain significance ★ ⚠ same condition
CHRDL1 p.Arg218Ter Pathogenic 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/chrdl1-p-glu69asp (accessed [today's date]).

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