Is SYNCRIP p.Glu163Asp (c.489G>C) pathogenic?

SYNCRIP p.Glu163Asp (c.489G>C) is classified Uncertain significance in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-01). AlphaMissense: likely pathogenic (0.998); Absent from gnomAD v4.1.

How common is SYNCRIP p.Glu163Asp (c.489G>C) in the general population?

SYNCRIP p.Glu163Asp (c.489G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SYNCRIP p.Glu163Asp (c.489G>C)?

AlphaMissense predicts likely pathogenic (score 0.998) — an in-silico prediction, not a clinical call.

SYNCRIP p.Glu163Asp

c.489G>C · rs2128301121 · VCV1311979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.998	likely pathogenic
REVEL	0.218	benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.96	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.76	loss · gain 0.41 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 18 kb · p 2.8e-22 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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.Glu163Asp
Coding: c.489G>C
MANE Select: NM_006372
dbSNP: rs2128301121
Type: single nucleotide variant
Location: chr6:85637243 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 163: the rrm 1 domain

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

Similar variants

SYNCRIP p.Ala216Thr Uncertain significance ★★ same type
SYNCRIP p.Asn243Ser Uncertain significance ★★ ⚠ same type
SYNCRIP p.Pro440Leu Uncertain significance ★★ ⚠ same type
SYNCRIP p.Pro508Leu Uncertain significance ★★ ⚠ same type
SYNCRIP p.Ser116Gly Uncertain significance ★★ ⚠ same type
SYNCRIP p.Glu612Val Likely benign ★★ ⚠ same type
SYNCRIP p.Arg446Ter Pathogenic ★ same type
SYNCRIP c.803-3C>A 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/syncrip-p-glu163asp (accessed [today's date]).

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