Is SMYD3 p.Val67= (c.201C>T) pathogenic?

SMYD3 p.Val67= (c.201C>T) is classified Benign in SMYD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-16). Common (popmax 7.64%, afr) — too common for a highly-penetrant pathogenic allele.

SMYD3 p.Val67=

Q: How common is SMYD3 p.Val67= (c.201C>T) in the general population?

SMYD3 p.Val67= (c.201C>T) is common (popmax 7.64%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.201C>T · rs11544849 · VCV775698

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.64%, 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 -2	GERP -4.5
Overall
CADD	0.858	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.64% African / African-American · 5,732/75,006 alleles

Filtering AF 7.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.41%

Overall 0.407% 6,568/1,614,122 alleles · common exomes 3,175/1,461,864 · genomes 3,393/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.64%	13
Admixed American	0.715%	140
Remaining individualsnot grpmax-eligible	0.498%	201
Middle Eastern	0.0825%	1,212
East Asian	0.0134%	7,480
South Asian	0.011%	9,108
European (non-Finnish)	0.00636%	15,734

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: SMYD3
Protein: p.Val67=
Coding: c.201C>T
MANE Select: NM_001167740
dbSNP: rs11544849
Type: single nucleotide variant
Location: chr1:246355058 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.36 · 34 PDB
Residue 67: the set domain

Full SMYD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMYD3 p.Val67Ile Uncertain significance ★ ⚠ same residue
SMYD3 c.813+8G>A Benign ★★ same type
SMYD3 p.Ala168Val Uncertain significance ★ ⚠ same type
SMYD3 p.Ala20Val Uncertain significance ★ same type
SMYD3 p.Ala389Thr Uncertain significance ★ ⚠ same type
SMYD3 p.Ala423Thr Uncertain significance ★ ⚠ same type
SMYD3 p.Arg103Gln Uncertain significance ★ ⚠ same type
SMYD3 p.Arg103Ter 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/smyd3-p-val67 (accessed [today's date]).

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