Is ELP4 p.Ser394Thr (c.1181G>C) pathogenic?

ELP4 p.Ser394Thr (c.1181G>C) is classified Benign/Likely benign in ELP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.2073); Low-frequency (popmax 1.37%, mid).

How common is ELP4 p.Ser394Thr (c.1181G>C) in the general population?

ELP4 p.Ser394Thr (c.1181G>C) is low-frequency (popmax 1.37%, mid) (gnomAD).

What do computational predictors say about ELP4 p.Ser394Thr (c.1181G>C)?

AlphaMissense predicts likely benign (score 0.2073) — an in-silico prediction, not a clinical call.

ELP4 p.Ser394Thr

c.1181G>C · rs3026404 · VCV707248

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2073 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2073	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -6.91	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 8.7	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 274 kb · p 0.85 · regional, not allelic
Overall
CADD	23.4	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 1.37% Middle Eastern · 83/6,058 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.626% 10,101/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.52%	40
Middle Easterngrpmax	1.37%	73
South Asian	1.27%	79
Ashkenazi Jewishnot grpmax-eligible	0.645%	155
European (non-Finnish)	0.645%	155
Remaining individualsnot grpmax-eligible	0.602%	166
Finnishnot grpmax-eligible	0.469%	213
Admixed American	0.401%	249
African / African-American	0.127%	790
East Asian	0.0579%	1,726

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: ELP4
Protein: p.Ser394Thr
Coding: c.1181G>C
MANE Select: NM_019040
dbSNP: rs3026404
Type: single nucleotide variant
Location: chr11:31783430 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49

Full ELP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAX6 p.Arg222Trp Pathogenic/Likely pathogenic ★★ same type
PAX6 p.Ter437Gln Pathogenic/Likely pathogenic ★★ same type
PAX6 p.Ter437Leu Pathogenic/Likely pathogenic ★★ same type
ELP4 p.Arg163His Uncertain significance ★★ ⚠ same type
ELP4 p.Arg31Ser Uncertain significance ★★ ⚠ same type
ELP4 p.Arg395His Uncertain significance ★★ ⚠ same type
ELP4 p.Asn244Ser Uncertain significance ★★ ⚠ same type
ELP4 p.Gln165Pro 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/elp4-p-ser394thr (accessed [today's date]).

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