Is SYNRG p.Ile702Val (c.2104A>G) pathogenic?

SYNRG p.Ile702Val (c.2104A>G) is classified Likely benign in SYNRG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely benign (0.0606); Rare (popmax 0.132%, mid).

How common is SYNRG p.Ile702Val (c.2104A>G) in the general population?

SYNRG p.Ile702Val (c.2104A>G) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about SYNRG p.Ile702Val (c.2104A>G)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

SYNRG p.Ile702Val

c.2104A>G · rs139017068 · VCV2259202

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.32	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 -8.9	GERP -4.5
Regional constraint	o/e 0.85	unconstrained · MANE · 66 kb · p 8.4e-08 · regional, not allelic
Overall
CADD	0.032	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 0.132% Middle Eastern · 8/6,060 alleles

Filtering AF 0.0917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0838%

Overall 0.03% 484/1,614,076 alleles · rare exomes 431/1,461,824 · genomes 53/152,252 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.361%	277
Middle Easterngrpmax	0.132%	758
Admixed American	0.113%	882
Remaining individualsnot grpmax-eligible	0.064%	1,563
South Asian	0.0549%	1,821
European (non-Finnish)	0.0176%	5,673
African / African-American	0.004%	25,006

Ashkenazi Jewish 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: SYNRG
Protein: p.Ile702Val
Coding: c.2104A>G
MANE Select: NM_007247
dbSNP: rs139017068
Type: single nucleotide variant
Location: chr17:37553619 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.74 · 1 PDB
Residue 702: the 'interaction with ap1g1' region

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

Similar variants

SYNRG c.372-1G>A Uncertain significance ★ same type
SYNRG c.3813+5G>A Uncertain significance ★ same type
SYNRG p.Ala1246Val Uncertain significance ★ ⚠ same type
SYNRG p.Ala1291Thr Uncertain significance ★ ⚠ same type
SYNRG p.Ala15Thr Uncertain significance ★ ⚠ same type
SYNRG p.Ala171Val Uncertain significance ★ ⚠ same type
SYNRG p.Ala17Val Uncertain significance ★ ⚠ same type
SYNRG p.Ala261Thr 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/synrg-p-ile702val (accessed [today's date]).

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