Is DHDH p.Ile197Ser (c.590T>G) pathogenic?

DHDH p.Ile197Ser (c.590T>G) is classified Uncertain significance in DHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). AlphaMissense: likely pathogenic (0.6708); Very rare (popmax 0.000937%, nfe).

How common is DHDH p.Ile197Ser (c.590T>G) in the general population?

DHDH p.Ile197Ser (c.590T>G) is very rare (popmax 0.000937%, nfe) (gnomAD).

What do computational predictors say about DHDH p.Ile197Ser (c.590T>G)?

AlphaMissense predicts likely pathogenic (score 0.6708) — an in-silico prediction, not a clinical call.

DHDH p.Ile197Ser

c.590T>G · rs1600087110 · VCV2322307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000937%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6708	likely pathogenic
REVEL	0.368	indeterminate
SaProt	LLR -10.13	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.26 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000937% European (non-Finnish) · 11/1,173,466 alleles

Filtering AF 0.000503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000368%

Overall 0.000685% 11/1,605,742 alleles · very rare

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: DHDH
Protein: p.Ile197Ser
Coding: c.590T>G
MANE Select: NM_014475
dbSNP: rs1600087110
Type: single nucleotide variant
Location: chr19:48939672 (GRCh38)
Gene constraint: LOEUF 1.275 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.19

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

Similar variants

DHDH p.Ala111Ser Uncertain significance ★ ⚠ same type
DHDH p.Ala134Thr Uncertain significance ★ ⚠ same type
DHDH p.Ala173Thr Uncertain significance ★ ⚠ same type
DHDH p.Ala70Ser Uncertain significance ★ ⚠ same type
DHDH p.Ala89Val Uncertain significance ★ ⚠ same type
DHDH p.Arg107His Uncertain significance ★ ⚠ same type
DHDH p.Arg107Ser Uncertain significance ★ ⚠ same type
DHDH p.Arg127His 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/dhdh-p-ile197ser (accessed [today's date]).

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