Is IL6 p.Asp162Val (c.485A>T) pathogenic?

IL6 p.Asp162Val (c.485A>T) is classified Benign in IL6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.1374); Low-frequency (popmax 1.03%, sas).

How common is IL6 p.Asp162Val (c.485A>T) in the general population?

IL6 p.Asp162Val (c.485A>T) is low-frequency (popmax 1.03%, sas) (gnomAD).

What do computational predictors say about IL6 p.Asp162Val (c.485A>T)?

AlphaMissense predicts likely benign (score 0.1374) — an in-silico prediction, not a clinical call.

IL6 p.Asp162Val

c.485A>T · rs2069860 · VCV777811

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1374 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1374	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.79	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 0.002	GERP -3.2
Regional constraint	o/e 1.06	unconstrained · MANE · 4,307 bp · p 0.34 · regional, not allelic
Overall
CADD	1.914	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 1.03% South Asian · 902/87,232 alleles

Filtering AF 0.978% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.956%

Overall 0.741% 11,666/1,573,798 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.73%	27
South Asiangrpmax	1.03%	97
European (non-Finnish)	0.833%	120
Finnishnot grpmax-eligible	0.77%	130
Remaining individualsnot grpmax-eligible	0.71%	141
Middle Eastern	0.204%	489
Admixed American	0.132%	760
African / African-American	0.127%	785
Ashkenazi Jewishnot grpmax-eligible	0.0388%	2,579
East Asian	0.00226%	44,156

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: IL6
Protein: p.Asp162Val
Coding: c.485A>T
MANE Select: NM_000600
dbSNP: rs2069860
Type: single nucleotide variant
Location: chr7:22731419 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 86.05 · 17 PDB
Residue 162: a UniProt-annotated variant site (in)

Full IL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL6 p.Leu61= Likely benign ★★ same type
IL6 p.Ser65= Likely benign ★★ same type
IL6 p.Ala40Asp Uncertain significance ★ ⚠ same type
IL6 p.Arg141Ile Uncertain significance ★ ⚠ same type
IL6 p.Arg196Ser Uncertain significance ★ ⚠ same type
IL6 p.Arg207Thr Uncertain significance ★ ⚠ same type
IL6 p.Asn183Lys Uncertain significance ★ ⚠ same type
IL6 p.Asn73Ser 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/il6-p-asp162val (accessed [today's date]).

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