Is SYNRG p.Arg344Gln (c.1031G>A) pathogenic?

SYNRG p.Arg344Gln (c.1031G>A) is classified Uncertain significance in SYNRG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.1114); Ultra-rare (popmax 0.0312%, eas).

How common is SYNRG p.Arg344Gln (c.1031G>A) in the general population?

SYNRG p.Arg344Gln (c.1031G>A) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about SYNRG p.Arg344Gln (c.1031G>A)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

SYNRG p.Arg344Gln

c.1031G>A · rs372011928 · VCV2323118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 66 kb · p 8.4e-08 · regional, not allelic
Overall
CADD	32.0	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 0.0312% East Asian · 14/44,886 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0052% 84/1,614,008 alleles · ultra-rare exomes 75/1,461,854 · genomes 9/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)	0.00508%	19,667
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
African / African-American	0.00267%	37,453

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.Arg344Gln
Coding: c.1031G>A
MANE Select: NM_007247
dbSNP: rs372011928
Type: single nucleotide variant
Location: chr17:37571858 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.74 · 1 PDB
Residue 344: the eh domain

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
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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-arg344gln (accessed [today's date]).

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