Is TTR p.Ser97Phe (c.290C>T) pathogenic?

TTR p.Ser97Phe (c.290C>T) is classified Pathogenic in TTR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-30). AlphaMissense: likely benign (0.2318); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TTR p.Ser97Phe (c.290C>T)?

TTR p.Ser97Phe (c.290C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TTR p.Ser97Phe (c.290C>T) in the general population?

TTR p.Ser97Phe (c.290C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTR p.Ser97Phe (c.290C>T)?

AlphaMissense predicts likely benign (score 0.2318) — an in-silico prediction, not a clinical call.

TTR p.Ser97Phe

c.290C>T · rs121918071 · VCV1797565

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2318 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2318	likely benign ⚠ discordant with ClinVar
REVEL	0.739	pathogenic-leaning
SaProt	LLR -12.17	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.73	unconstrained · MANE · 6,769 bp · p 0.00021 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTR
Protein: p.Ser97Phe
Coding: c.290C>T
MANE Select: NM_000371
dbSNP: rs121918071
Type: single nucleotide variant
Location: chr18:31595209 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.74 · 493 PDB
Residue 97: an α-helix; a UniProt-annotated variant site (in amyld1; amyloid polyneuropathy)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTR p.Ser97Tyr Pathogenic/Likely pathogenic ★★ ⚠ same residue
TTR p.Ala39Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TTR p.Ala56Pro Pathogenic/Likely pathogenic ★★ same condition
TTR p.Ala65Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
TTR p.Arg54Thr Pathogenic/Likely pathogenic ★★ same condition
TTR p.Asp38Asn Pathogenic ★★ ⚠ same condition
TTR p.Asp58Ala Pathogenic ★★ ⚠ same condition
TTR p.Asp58His 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-ser97phe (accessed [today's date]).

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