Is DHX57 p.Gly485Ser (c.1453G>A) pathogenic?

DHX57 p.Gly485Ser (c.1453G>A) is classified Uncertain significance in DHX57 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0712); Very rare (popmax 0.00526%, nfe).

How common is DHX57 p.Gly485Ser (c.1453G>A) in the general population?

DHX57 p.Gly485Ser (c.1453G>A) is very rare (popmax 0.00526%, nfe) (gnomAD).

What do computational predictors say about DHX57 p.Gly485Ser (c.1453G>A)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

DHX57 p.Gly485Ser

c.1453G>A · VCV3501723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00526%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.38	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 -0.046, phastCons 0.99
Regional constraint	o/e 1.11	unconstrained · MANE · 70 kb · p 5.6e-06 · regional, not allelic
Overall
CADD	16.19	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

Grpmax group 0.00526% European (non-Finnish) · 62/1,179,826 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00409% 66/1,613,054 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00526%	19,029
East Asian	0.00223%	44,842
South Asian	0.0022%	45,376
Admixed American	0.00167%	59,764

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: DHX57
Protein: p.Gly485Ser
Coding: c.1453G>A
MANE Select: NM_198963
Type: single nucleotide variant
Location: chr2:38858795 (GRCh38)
Gene constraint: LOEUF 0.742 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.68

Full DHX57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX57 p.Ala1014Val Uncertain significance ★ ⚠ same type
DHX57 p.Ala1084Thr Uncertain significance ★ ⚠ same type
DHX57 p.Ala1115Val Uncertain significance ★ ⚠ same type
DHX57 p.Ala1117Gly Uncertain significance ★ ⚠ same type
DHX57 p.Ala1117Ser Uncertain significance ★ ⚠ same type
DHX57 p.Ala1127Val Uncertain significance ★ ⚠ same type
DHX57 p.Ala1207Thr Uncertain significance ★ ⚠ same type
DHX57 p.Ala125Asp 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/dhx57-p-gly485ser (accessed [today's date]).

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