Is ESD p.Thr116= (c.348C>T) pathogenic?

ESD p.Thr116= (c.348C>T) is classified Benign/Likely benign in ESD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-01). Rare (popmax 0.685%, nfe).

How common is ESD p.Thr116= (c.348C>T) in the general population?

ESD p.Thr116= (c.348C>T) is rare (popmax 0.685%, nfe) (gnomAD).

ESD p.Thr116=

c.348C>T · rs35111834 · VCV784270

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.685%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.049	GERP -2.4, phastCons 0.023
Overall
CADD	3.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.685% European (non-Finnish) · 8,073/1,178,668 alleles

Filtering AF 0.672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.667%

Overall 0.537% 8,663/1,612,056 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.37%	19
European (non-Finnish)grpmax	0.685%	146
Remaining individualsnot grpmax-eligible	0.428%	234
Admixed American	0.234%	427
African / African-American	0.114%	881
Ashkenazi Jewishnot grpmax-eligible	0.0474%	2,108
Finnishnot grpmax-eligible	0.0469%	2,133
South Asian	0.0044%	22,753
East Asian	0.00223%	44,832

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ESD
Protein: p.Thr116=
Coding: c.348C>T
MANE Select: NM_001984
dbSNP: rs35111834
Type: single nucleotide variant
Location: chr13:46782700 (GRCh38)
Gene constraint: LOEUF 1.515 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.28 · 1 PDB
Residue 116: an α-helix

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

Similar variants

ESD p.Asp271= Benign ★★ same type
ESD p.Ala173Pro Uncertain significance ★ ⚠ same type
ESD p.Ala242Val Uncertain significance ★ ⚠ same type
ESD p.Ala33Gly Uncertain significance ★ ⚠ same type
ESD p.Arg119Lys Uncertain significance ★ ⚠ same type
ESD p.Arg253Gln Uncertain significance ★ ⚠ same type
ESD p.Asn135Ser Uncertain significance ★ ⚠ same type
ESD p.Asp217Gly 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/esd-p-thr116 (accessed [today's date]).

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