Is TTR p.Asp38= (c.114T>C) pathogenic?

TTR p.Asp38= (c.114T>C) is classified Likely benign in TTR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Very rare (popmax 0.000424%, nfe); Associated with amyloidosis, hereditary systemic 1.

What condition is associated with TTR p.Asp38= (c.114T>C)?

TTR p.Asp38= (c.114T>C) is associated with amyloidosis, hereditary systemic 1 (ClinVar).

How common is TTR p.Asp38= (c.114T>C) in the general population?

TTR p.Asp38= (c.114T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Hereditary ATTR amyloidosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TTR p.Asp38=

c.114T>C · rs779619795 · VCV756250

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

amyloidosis, hereditary systemic 1

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 -2.3	GERP -3.3
Overall
CADD	2.095	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,972 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,120 alleles · very rare exomes 5/1,461,802 · genomes 0/152,318 · joint denominator

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: TTR
Protein: p.Asp38=
Coding: c.114T>C
MANE Select: NM_000371
dbSNP: rs779619795
Type: single nucleotide variant
Location: chr18:31592940 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.74 · 493 PDB
Residue 38: a β-strand; a UniProt-annotated variant site (in amyld1; amyloid polyneuropathy); a UniProt-annotated variant site (in amyld1; leptomeningeal amyloidosis; leads to unfolding and exposure of n-118 to glycosylation by stt3b and subsequent degradation by the erad pathway)

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

Disease context

amyloidosis, hereditary systemic 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary ATTR amyloidosis (Orphanet):

Inheritance: Autosomal dominant
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

TTR p.Asp38Asn Pathogenic ★★ ⚠ same residue
TTR p.Asp38Glu Pathogenic ★★ ⚠ same residue
TTR p.Asp38Gly Pathogenic ★★ same residue
TTR p.Asp38Tyr Pathogenic ★ same residue
TTR p.Ala117Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
TTR p.Ala39Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TTR p.Ala56Pro Pathogenic/Likely pathogenic ★★ same condition
TTR p.Ala65Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition

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/ttr-p-asp38 (accessed [today's date]).

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