Is CRYGA p.Ser86Thr (c.257G>C) pathogenic?

CRYGA p.Ser86Thr (c.257G>C) is classified Uncertain significance in CRYGA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely benign (0.0783); Absent from gnomAD v4.1.

How common is CRYGA p.Ser86Thr (c.257G>C) in the general population?

CRYGA p.Ser86Thr (c.257G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYGA p.Ser86Thr (c.257G>C)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

CRYGA p.Ser86Thr

c.257G>C · VCV3497452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.36	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.5	GERP 1.5, phastCons 0.99
Regional constraint	o/e 1.16	unconstrained · MANE · 2,749 bp · p 0.016 · regional, not allelic
Overall
CADD	20.2	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: CRYGA
Protein: p.Ser86Thr
Coding: c.257G>C
MANE Select: NM_014617
Type: single nucleotide variant
Location: chr2:208161072 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.14
Residue 86: the 'connecting peptide' region

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

Similar variants

CRYGA p.Ser86Asn Uncertain significance ★ ⚠ same residue
CRYGA p.Arg99Ter Benign ★★ same type
CRYGA p.Ala110Thr Uncertain significance ★ ⚠ same type
CRYGA p.Arg140Gln Uncertain significance ★ ⚠ same type
CRYGA p.Arg140Leu Uncertain significance ★ ⚠ same type
CRYGA p.Arg142Gln Uncertain significance ★ ⚠ same type
CRYGA p.Arg153Ser Uncertain significance ★ ⚠ same type
CRYGA p.Arg15His 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/cryga-p-ser86thr (accessed [today's date]).

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