Is SYNCRIP p.Glu121Lys (c.361G>A) pathogenic?

SYNCRIP p.Glu121Lys (c.361G>A) is classified Uncertain significance in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely pathogenic (0.9363); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SYNCRIP p.Glu121Lys (c.361G>A)?

SYNCRIP p.Glu121Lys (c.361G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SYNCRIP p.Glu121Lys (c.361G>A) in the general population?

SYNCRIP p.Glu121Lys (c.361G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SYNCRIP p.Glu121Lys (c.361G>A)?

AlphaMissense predicts likely pathogenic (score 0.9363) — an in-silico prediction, not a clinical call.

SYNCRIP p.Glu121Lys

c.361G>A · VCV3803392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9363	likely pathogenic
REVEL	0.324	indeterminate
SaProt	LLR -11.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 18 kb · p 2.8e-22 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: SYNCRIP
Protein: p.Glu121Lys
Coding: c.361G>A
MANE Select: NM_006372
Type: single nucleotide variant
Location: chr6:85640235 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SYNCRIP p.Ala216Thr Uncertain significance ★★ same condition
SYNCRIP p.Asn243Ser Uncertain significance ★★ ⚠ same condition
SYNCRIP p.Pro440Leu Uncertain significance ★★ ⚠ same condition
SYNCRIP p.Pro508Leu Uncertain significance ★★ ⚠ same condition
SYNCRIP p.Ser116Gly Uncertain significance ★★ ⚠ same condition
SYNCRIP p.Glu612Val Likely benign ★★ ⚠ same condition
SYNCRIP p.Ala346Thr Uncertain significance ★ ⚠ same condition
SYNCRIP p.Ala357Val Uncertain significance ★ ⚠ 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/syncrip-p-glu121lys (accessed [today's date]).

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