Is FYN p.His54= (c.162C>T) pathogenic?

FYN p.His54= (c.162C>T) is classified Likely benign in FYN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). Ultra-rare (popmax 0.0493%, afr).

How common is FYN p.His54= (c.162C>T) in the general population?

FYN p.His54= (c.162C>T) is ultra-rare (popmax 0.0493%, afr) (gnomAD).

FYN p.His54=

c.162C>T · VCV3280271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, afr)

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 -3.2	GERP -5.3
Overall
CADD	1.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% African / African-American · 37/75,032 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0323%

Overall 0.00384% 62/1,614,170 alleles · ultra-rare exomes 42/1,461,890 · genomes 20/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0493%	2,028
Middle Eastern	0.033%	3,031
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.0011%	90,772

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: FYN
Protein: p.His54=
Coding: c.162C>T
MANE Select: NM_002037
Type: single nucleotide variant
Location: chr6:111719890 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.62 · 53 PDB

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

Similar variants

FYN p.Asp506Glu Benign ★★ same type
FYN c.344+1G>A Uncertain significance ★ same type
FYN p.Ala55Thr Uncertain significance ★ ⚠ same type
FYN p.Arg123Cys Uncertain significance ★ ⚠ same type
FYN p.Arg161Ter Uncertain significance ★ same type
FYN p.Arg29Cys Uncertain significance ★ ⚠ same type
FYN p.Asp8Glu Uncertain significance ★ ⚠ same type
FYN p.Asp92Asn 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/fyn-p-his54 (accessed [today's date]).

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