Is CHRDL2 p.Ala215Val (c.644C>T) pathogenic?

CHRDL2 p.Ala215Val (c.644C>T) is classified Uncertain significance in CHRDL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-15). AlphaMissense: likely benign (0.0826); Absent from gnomAD v4.1.

How common is CHRDL2 p.Ala215Val (c.644C>T) in the general population?

CHRDL2 p.Ala215Val (c.644C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRDL2 p.Ala215Val (c.644C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

CHRDL2 p.Ala215Val

c.644C>T · rs2547266816 · VCV2398791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,006)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.75	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 9.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 34 kb · p 0.061 · regional, not allelic
Overall
CADD	19.69	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

No allele count reported in gnomAD v4.1 (AN 1,600,006). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHRDL2
Protein: p.Ala215Val
Coding: c.644C>T
MANE Select: NM_001278473
dbSNP: rs2547266816
Type: single nucleotide variant
Location: chr11:74704593 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.31
Residue 215: the 'disordered' region

Full CHRDL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRDL2 c.*3A>G Uncertain significance ★ same type
CHRDL2 p.Ala173Thr Uncertain significance ★ ⚠ same type
CHRDL2 p.Ala205Thr Uncertain significance ★ ⚠ same type
CHRDL2 p.Ala221Thr Uncertain significance ★ ⚠ same type
CHRDL2 p.Ala360Thr Uncertain significance ★ ⚠ same type
CHRDL2 p.Ala67Gly Uncertain significance ★ ⚠ same type
CHRDL2 p.Ala67Thr Uncertain significance ★ ⚠ same type
CHRDL2 p.Arg228His Uncertain significance ★ ⚠ same type

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/chrdl2-p-ala215val (accessed [today's date]).

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