Is DPH6 p.Met161Ile (c.483G>C) pathogenic?

DPH6 p.Met161Ile (c.483G>C) is classified Likely benign in DPH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1122); Ultra-rare (popmax 0.0117%, amr).

How common is DPH6 p.Met161Ile (c.483G>C) in the general population?

DPH6 p.Met161Ile (c.483G>C) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about DPH6 p.Met161Ile (c.483G>C)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

DPH6 p.Met161Ile

c.483G>C · VCV4014567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -4.00	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 -3.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 174 kb · p 0.78 · regional, not allelic
Overall
CADD	0.749	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

Grpmax group 0.0117% Admixed American · 7/59,854 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000434% 7/1,612,874 alleles · ultra-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: DPH6
Protein: p.Met161Ile
Coding: c.483G>C
MANE Select: NM_080650
Type: single nucleotide variant
Location: chr15:35450707 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.85

Full DPH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH6 p.Met161Val Likely benign ★ same residue
DPH6 p.Gly41Glu Benign ★★ same type
DPH6 p.Ala5Ser Uncertain significance ★ ⚠ same type
DPH6 p.Arg123His Uncertain significance ★ ⚠ same type
DPH6 p.Arg241His Uncertain significance ★ ⚠ same type
DPH6 p.Arg2Trp Uncertain significance ★ ⚠ same type
DPH6 p.Asp173Ala Uncertain significance ★ ⚠ same type
DPH6 p.Asp173His 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/dph6-p-met161ile (accessed [today's date]).

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