Is CROCC p.Ala679Val (c.2036C>T) pathogenic?

CROCC p.Ala679Val (c.2036C>T) is classified Uncertain significance in CROCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0907); Absent from gnomAD v4.1.

How common is CROCC p.Ala679Val (c.2036C>T) in the general population?

CROCC p.Ala679Val (c.2036C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CROCC p.Ala679Val (c.2036C>T)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

CROCC p.Ala679Val

c.2036C>T · VCV4234423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.28	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 0.23	GERP 0.64, phastCons 0.008
Regional constraint	o/e 0.29	constrained · MANE · 1,316 bp · p 3.5e-08 · regional, not allelic
Overall
CADD	20.9	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: CROCC
Protein: p.Ala679Val
Coding: c.2036C>T
MANE Select: NM_014675
Type: single nucleotide variant
Location: chr1:16945506 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 2 PDB

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

Similar variants

CROCC p.Arg1094Trp Uncertain significance ★★ ⚠ same type
CROCC p.Asp1119His Uncertain significance ★★ ⚠ same type
CROCC p.Gly486Arg Uncertain significance ★★ ⚠ same type
CROCC p.Arg1729Gln Likely benign ★★ same type
CROCC p.Arg1908Cys Benign ★★ ⚠ same type
CROCC p.Arg675His Benign ★★ same type
CROCC p.Arg691His Benign ★★ same type
CROCC p.Arg903Ser Benign/Likely benign ★★ 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/crocc-p-ala679val (accessed [today's date]).

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