Is SRC p.Glu283= (c.849G>A) pathogenic?

SRC p.Glu283= (c.849G>A) is classified Likely benign in SRC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-30). Ultra-rare (popmax 0.0212%, mid); Associated with SRC-related disorder.

What condition is associated with SRC p.Glu283= (c.849G>A)?

SRC p.Glu283= (c.849G>A) is associated with SRC-related disorder (ClinVar).

How common is SRC p.Glu283= (c.849G>A) in the general population?

SRC p.Glu283= (c.849G>A) is ultra-rare (popmax 0.0212%, mid) (gnomAD).

SRC p.Glu283=

c.849G>A · rs757188731 · VCV3042787

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0212%, mid)

Conditions

SRC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.60	donor loss · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP -3.7, phastCons 1
Overall
CADD	10.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0212% Middle Eastern · 1/4,712 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00824%

Overall 0.00292% 47/1,610,176 alleles · ultra-rare exomes 45/1,457,972 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0212%	4,712
South Asian	0.0165%	6,046
Finnishnot grpmax-eligible	0.00791%	12,636
Admixed American	0.00334%	29,926
Remaining individualsnot grpmax-eligible	0.00321%	31,108
European (non-Finnish)	0.00187%	53,610

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: SRC
Protein: p.Glu283=
Coding: c.849G>A
MANE Select: NM_198291
dbSNP: rs757188731
Type: single nucleotide variant
Location: chr20:37397844 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 283: the protein kinase domain; a β-strand; a binding site

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

Disease context

SRC-related disorder

Similar variants

SRC p.Glu527Lys Pathogenic/Likely pathogenic ★★ same condition
SRC c.450-8A>T Likely benign same condition
SRC p.Phe175= Likely benign same condition
SRC p.Pro532= Likely benign same condition
SRC p.Ser212= Likely benign same condition
SRC p.Glu492Lys Uncertain significance ★★ ⚠ same type
SRC c.1117-180C>T Benign ★★ same type
SRC c.1117-9C>T Likely 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/src-p-glu283 (accessed [today's date]).

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