Is LYN p.Asp138= (c.414C>T) pathogenic?

LYN p.Asp138= (c.414C>T) is classified Likely benign in LYN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-05). Ultra-rare (popmax 0.0134%, eas).

How common is LYN p.Asp138= (c.414C>T) in the general population?

LYN p.Asp138= (c.414C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

LYN p.Asp138=

c.414C>T · rs767213766 · VCV1588012

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 -6.2	GERP -3.7
Overall
CADD	0.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,876 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00248% 40/1,613,718 alleles · ultra-rare exomes 37/1,461,634 · genomes 3/152,084 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,479
Admixed American	0.0133%	7,500
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.00329%	30,362
European (non-Finnish)	0.0017%	58,990
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00134%	74,878

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.Asp138=
Coding: c.414C>T
MANE Select: NM_002350
dbSNP: rs767213766
Type: single nucleotide variant
Location: chr8:55950711 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 6 PDB
Residue 138: the sh2 domain

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-asp138 (accessed [today's date]).

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