Is LYN p.Ile358= (c.1074C>T) pathogenic?

LYN p.Ile358= (c.1074C>T) is classified Benign in LYN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele.

LYN p.Ile358=

Q: How common is LYN p.Ile358= (c.1074C>T) in the general population?

LYN p.Ile358= (c.1074C>T) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1074C>T · rs2227978 · VCV783841

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -3.7
Overall
CADD	6.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% African / African-American · 7,551/74,944 alleles

Filtering AF 9.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.81%

Overall 0.534% 8,622/1,613,392 alleles · common exomes 4,193/1,461,206 · genomes 4,429/152,186 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Admixed American	0.708%	141
Remaining individualsnot grpmax-eligible	0.667%	150
Middle Eastern	0.314%	319
South Asian	0.0253%	3,960
European (non-Finnish)	0.0158%	6,341
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598

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: LYN
Protein: p.Ile358=
Coding: c.1074C>T
MANE Select: NM_002350
dbSNP: rs2227978
Type: single nucleotide variant
Location: chr8:55998369 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 6 PDB
Residue 358: the protein kinase domain; an α-helix

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

Similar variants

LYN p.Ala150Thr Uncertain significance ★★ ⚠ same type
LYN p.Ala70Thr Uncertain significance ★★ ⚠ same type
LYN p.Arg360Trp Uncertain significance ★★ ⚠ same type
LYN p.Glu47Asp Uncertain significance ★★ ⚠ same type
LYN p.Ile227Val Uncertain significance ★★ ⚠ same type
LYN p.Ser333Asn Uncertain significance ★★ same type
LYN p.Thr30Ala Uncertain significance ★★ ⚠ same type
LYN p.Val45Ile 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/lyn-p-ile358 (accessed [today's date]).

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