Is CHRD p.Val682Ala (c.2045T>C) pathogenic?

CHRD p.Val682Ala (c.2045T>C) is classified Uncertain significance in CHRD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.0639); Very rare (popmax 0.00577%, nfe).

How common is CHRD p.Val682Ala (c.2045T>C) in the general population?

CHRD p.Val682Ala (c.2045T>C) is very rare (popmax 0.00577%, nfe) (gnomAD).

What do computational predictors say about CHRD p.Val682Ala (c.2045T>C)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

CHRD p.Val682Ala

c.2045T>C · rs762607770 · VCV2374243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00577%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.29	GERP -2.1
Regional constraint	o/e 0.92	unconstrained · MANE · 9,100 bp · p 0.0047 · regional, not allelic
Overall
CADD	4.545	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

Grpmax group 0.00577% European (non-Finnish) · 68/1,177,646 alleles

Filtering AF 0.00463% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00443% 71/1,603,992 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00577%	17,318
Remaining individualsnot grpmax-eligible	0.00322%	31,008
African / African-American	0.00134%	74,602

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: CHRD
Protein: p.Val682Ala
Coding: c.2045T>C
MANE Select: NM_003741
dbSNP: rs762607770
Type: single nucleotide variant
Location: chr3:184386604 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95 · 3 PDB
Residue 682: the 'disordered' region

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

Similar variants

CHRD p.Gln608= Benign ★★ same type
CHRD p.Gly387Ser Benign ★★ same type
CHRD p.Pro772= Benign ★★ same type
CHRD p.Thr301= Benign ★★ same type
CHRD p.Thr457Ser Likely benign ★★ same type
CHRD p.Ala251Glu Uncertain significance ★ ⚠ same type
CHRD p.Ala251Thr Uncertain significance ★ ⚠ same type
CHRD p.Ala27Pro 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/chrd-p-val682ala (accessed [today's date]).

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