Is SYK p.Pro110Ser (c.328C>T) pathogenic?

SYK p.Pro110Ser (c.328C>T) is classified Likely benign in SYK (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-07). AlphaMissense: likely benign (0.3368); Ultra-rare (popmax 0.0103%, nfe).

How common is SYK p.Pro110Ser (c.328C>T) in the general population?

SYK p.Pro110Ser (c.328C>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about SYK p.Pro110Ser (c.328C>T)?

AlphaMissense predicts likely benign (score 0.3368) — an in-silico prediction, not a clinical call.

SYK p.Pro110Ser

c.328C>T · VCV4848809

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3368 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3368	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -10.82	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 31 kb · p 7.2e-08 · regional, not allelic
Overall
CADD	22.6	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 0.0103% European (non-Finnish) · 122/1,180,014 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.00824% 133/1,614,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,672
Remaining individualsnot grpmax-eligible	0.0096%	10,418
African / African-American	0.004%	25,021
Admixed American	0.00167%	60,028
Finnishnot grpmax-eligible	0.00156%	64,046

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: SYK
Protein: p.Pro110Ser
Coding: c.328C>T
MANE Select: NM_003177
Type: single nucleotide variant
Location: chr9:90844226 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.52 · 93 PDB
Residue 110: the 'interdomain a' region; an α-helix

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

Similar variants

SYK p.Glu473Gln Uncertain significance ★★ ⚠ same type
SYK c.1182-4G>A Benign ★★ same type
SYK c.1182-7C>A Benign ★★ same type
SYK c.1182-7C>G Benign ★★ same type
SYK c.1582-16T>A Benign ★★ same type
SYK c.796+20G>C Benign/Likely benign ★★ same type
SYK p.Arg434= Benign ★★ same type
SYK p.Asn499= Benign ★★ 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/syk-p-pro110ser (accessed [today's date]).

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