Is SYNCRIP p.Glu327Val (c.980A>T) pathogenic?

SYNCRIP p.Glu327Val (c.980A>T) is classified Uncertain significance in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.8769); Absent from gnomAD v4.1.

How common is SYNCRIP p.Glu327Val (c.980A>T) in the general population?

SYNCRIP p.Glu327Val (c.980A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SYNCRIP p.Glu327Val (c.980A>T)?

AlphaMissense predicts likely pathogenic (score 0.8769) — an in-silico prediction, not a clinical call.

SYNCRIP p.Glu327Val

c.980A>T · VCV4681065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8769	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	LLR -10.68	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.56	donor loss, 28 bp away · masked 0 · deltas
Pangolin	Δ0.35	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 3,768 bp · p 3.9e-16 · regional, not allelic
Overall
CADD	25.8	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.Glu327Val
Coding: c.980A>T
MANE Select: NM_006372
Type: single nucleotide variant
Location: chr6:85622510 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 327: a turn

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-glu327val (accessed [today's date]).

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