Is DDIAS p.Phe146Leu (c.438C>A) pathogenic?

DDIAS p.Phe146Leu (c.438C>A) is classified Uncertain significance in DDIAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.3931); Absent from gnomAD v4.1.

How common is DDIAS p.Phe146Leu (c.438C>A) in the general population?

DDIAS p.Phe146Leu (c.438C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDIAS p.Phe146Leu (c.438C>A)?

AlphaMissense predicts ambiguous (score 0.3931) — an in-silico prediction, not a clinical call.

DDIAS p.Phe146Leu

c.438C>A · rs2495855633 · VCV3080754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3931	ambiguous · top 8% in DDIAS
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.28	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -0.18, phastCons 0.001
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.0043 · regional, not allelic
Overall
CADD	12.38	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: DDIAS
Protein: p.Phe146Leu
Coding: c.438C>A
MANE Select: NM_145018
dbSNP: rs2495855633
Type: single nucleotide variant
Location: chr11:82931776 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 43.31

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

Similar variants

DDIAS p.Ala14Thr Uncertain significance ★ ⚠ same type
DDIAS p.Ala260Val Uncertain significance ★ ⚠ same type
DDIAS p.Ala389Ser Uncertain significance ★ ⚠ same type
DDIAS p.Ala402Val Uncertain significance ★ ⚠ same type
DDIAS p.Ala438Gly Uncertain significance ★ ⚠ same type
DDIAS p.Ala478Asp Uncertain significance ★ ⚠ same type
DDIAS p.Ala675Gly Uncertain significance ★ ⚠ same type
DDIAS p.Ala927Val 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/ddias-p-phe146leu (accessed [today's date]).

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