Is SYNCRIP p.Lys312Asn (c.936G>T) pathogenic?

SYNCRIP p.Lys312Asn (c.936G>T) is classified Uncertain significance in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: likely pathogenic (0.9728); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SYNCRIP p.Lys312Asn (c.936G>T)?

SYNCRIP p.Lys312Asn (c.936G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SYNCRIP p.Lys312Asn (c.936G>T) in the general population?

SYNCRIP p.Lys312Asn (c.936G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SYNCRIP p.Lys312Asn (c.936G>T)?

AlphaMissense predicts likely pathogenic (score 0.9728) — an in-silico prediction, not a clinical call.

SYNCRIP p.Lys312Asn

c.936G>T · VCV3451864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9728	likely pathogenic
REVEL	0.193	benign-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -2.1, phastCons 0.43
Regional constraint	o/e 0.34	constrained · MANE · 3,768 bp · p 3.9e-16 · regional, not allelic
Overall
CADD	21.1	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 0.000124% 2/1,614,180 alleles · very rare exomes 2/1,461,894 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	8.47e-05%	1,180,038

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SYNCRIP
Protein: p.Lys312Asn
Coding: c.936G>T
MANE Select: NM_006372
Type: single nucleotide variant
Location: chr6:85622554 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 312: the rrm 2 domain

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-lys312asn (accessed [today's date]).

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