Is DPH7 p.Ile77Met (c.231T>G) pathogenic?

DPH7 p.Ile77Met (c.231T>G) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.0761); Absent from gnomAD v4.1.

How common is DPH7 p.Ile77Met (c.231T>G) in the general population?

DPH7 p.Ile77Met (c.231T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPH7 p.Ile77Met (c.231T>G)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

DPH7 p.Ile77Met

c.231T>G · rs1228320349 · VCV3085497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -5.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -2.6
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	0.359	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: DPH7
Protein: p.Ile77Met
Coding: c.231T>G
MANE Select: NM_138778
dbSNP: rs1228320349
Type: single nucleotide variant
Location: chr9:137577526 (GRCh38)
Gene constraint: LOEUF 1.37 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.62

Full DPH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH7 p.Ile77Val Uncertain significance ★ ⚠ same residue
DPH7 p.Ala105Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala16Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala193Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Pro Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala427Thr 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/dph7-p-ile77met (accessed [today's date]).

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