Is SYNCRIP p.Ile234Val (c.700A>G) pathogenic?

SYNCRIP p.Ile234Val (c.700A>G) is classified Uncertain significance in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.142); Very rare (popmax 0.000254%, nfe).

How common is SYNCRIP p.Ile234Val (c.700A>G) in the general population?

SYNCRIP p.Ile234Val (c.700A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about SYNCRIP p.Ile234Val (c.700A>G)?

AlphaMissense predicts likely benign (score 0.142) — an in-silico prediction, not a clinical call.

SYNCRIP p.Ile234Val

c.700A>G · rs2128286909 · VCV1685156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.142 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.142	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 18 kb · p 2.8e-22 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,894 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,844 alleles · very rare exomes 3/1,461,588 · genomes 0/152,256 · joint denominator

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.Ile234Val
Coding: c.700A>G
MANE Select: NM_006372
dbSNP: rs2128286909
Type: single nucleotide variant
Location: chr6:85624079 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 234: the rrm 1 domain

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

Similar variants

SYNCRIP p.Ile234fs Pathogenic ★ same residue
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

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-ile234val (accessed [today's date]).

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